The document discusses challenges in implementing rheumatoid arthritis (RA) treatment guidelines in Indonesia. It notes barriers patients face in accessing appropriate care, including delays in diagnosis, variability in provider knowledge and competencies, access to healthcare facilities, and delays starting disease-modifying antirheumatic drugs (DMARDs). It also discusses challenges implementing guidelines, such as limited guideline availability and accessibility. The main considerations in determining RA treatment are a patient's disease activity, damage, comorbidities, drug efficacy, safety profiles, and drug availability in formularies. Pain reduction is an important but not sole treatment goal.
Opioids are commonly added to local anaesthetic for operations performed under epidural.
Neuraxial opioids improve the quality of intraoperative analgesia, delay regression of sensory blockade prolong postoperative analgesia.
Multiple trials have shown that the addition of opioids to local anaesthetic solutions significantly improves pain relief after thoracic, abdominal and orthopaedic surgery.
disampaikan dalam acara: Seminar STIE ST Pignatelli Surakarta, Selasa 29 Maret 2016, pk 13.00-16.00. Gedung Aula STIE St Pignatelli Jl. Duwet no.1 Karangasem, Laweyan, Surakarta
Yulita - Dukungan Regulasi bagi Penguatan PPK primerInsan Adiwibowo
Materi ini membahas bagaimana dukungan regulasi dapat membantu penyelenggaraan layanan kesehatan di PPK Primer sebagai gatekeeper kesehatan masyarakat.
Opioids are commonly added to local anaesthetic for operations performed under epidural.
Neuraxial opioids improve the quality of intraoperative analgesia, delay regression of sensory blockade prolong postoperative analgesia.
Multiple trials have shown that the addition of opioids to local anaesthetic solutions significantly improves pain relief after thoracic, abdominal and orthopaedic surgery.
disampaikan dalam acara: Seminar STIE ST Pignatelli Surakarta, Selasa 29 Maret 2016, pk 13.00-16.00. Gedung Aula STIE St Pignatelli Jl. Duwet no.1 Karangasem, Laweyan, Surakarta
Yulita - Dukungan Regulasi bagi Penguatan PPK primerInsan Adiwibowo
Materi ini membahas bagaimana dukungan regulasi dapat membantu penyelenggaraan layanan kesehatan di PPK Primer sebagai gatekeeper kesehatan masyarakat.
UPAYA PENINGKATAN KUALITAS PELAYANAN KES. IBU BERSALIN DAN NIFASDokter Tekno
Peningkatan Persalinan di Fasilitas Pelayanan Kesehatan pada Kabupaten Fokus di Provinsi Fokus dalam rangka Orientasi Pelayanan Persalinan dan Nifas Bagi Tenaga Kesehatan Puskesmas
Most people who have rheumatoid arthritis take some type of medication. Medications for RA typically fall into five categories:
Non-steroidal anti-inflammatory drugs (NSAIDs);
steroids;
disease-modifying anti-rheumatic drugs (DMARDS); biologics;
and janus kinase (JAK) inhibitors.
When prescribing a medication, a physician will take into account the patient’s age, disease activity, and other medical conditions, but each patient is unique. Figuring out which medication or combination of medications work best for an individual can be challenging and often requires a process of trial and error.
UPAYA PENINGKATAN KUALITAS PELAYANAN KES. IBU BERSALIN DAN NIFASDokter Tekno
Peningkatan Persalinan di Fasilitas Pelayanan Kesehatan pada Kabupaten Fokus di Provinsi Fokus dalam rangka Orientasi Pelayanan Persalinan dan Nifas Bagi Tenaga Kesehatan Puskesmas
Most people who have rheumatoid arthritis take some type of medication. Medications for RA typically fall into five categories:
Non-steroidal anti-inflammatory drugs (NSAIDs);
steroids;
disease-modifying anti-rheumatic drugs (DMARDS); biologics;
and janus kinase (JAK) inhibitors.
When prescribing a medication, a physician will take into account the patient’s age, disease activity, and other medical conditions, but each patient is unique. Figuring out which medication or combination of medications work best for an individual can be challenging and often requires a process of trial and error.
TREATMENT RESISTANT DEPRESSION IS A AREA THAT IS NOT EXPLORED MUCH, BUT IT REALLY NEEDS LOT OF ATTENTION AS IT IS ONE OF THE MOST COMMON OBSTACLE IN ACHIEVING COMPLETE REMISSION IN DEPRESSION
Case # 29- The depressed man who thought he was out of options. .docxannandleola
Case # 29- The depressed man who thought he was out of options.
Depression has become a common mental disorder in our elderly population. This has caused a global concern for occur, geriatric patients, as depression often results in a significant burden for families as well as communities. Elderly people who suffer from depression may have an inferior baseline and record for medical assessments than those individuals without depression. Despite consistent evidence of the effectiveness of antidepressants for many with depression,
3
particularly those with more severe depression, remission rates are disappointingly low. An AHRQ-sponsored report found that only 46% of patients experienced remission from depression during 6 to 12 weeks of treatment with second-generation antidepressants. One major reason for this issue is non-adherence to medications and treatment plans. Studies have shown that patients' age, race and ethnicity are consistently associated with predictions of outcomes. (Rossom et al., 2016).
This case study involves a 69-year old man whose chief complaint is unremitting, chronic depression. After several years of medications and treatments, he feels hopeless for a recovery from his chronic depression. This assignments seeks to explore his family and social support systems, diagnostic testing, differential diagnosis and pharmacologic treatment options for this patient.
Questions for the client
How have you been sleeping lately?
How many times in the last week have you had feelings of hopelessness?
Are you having thoughts of harming yourself? Do you have a plan?
These questions are an important yet simple place to start when treating patients. Sleep disturbances plague much of the world's population and have shown to be a major indicator for mental health issues. Changes in sleep neurophysiology are often observed in depressive patients, and impaired sleep is, in many cases, the chief complaint of depression (Armitage, 2007). Depressed patients with sleep disturbance are likely to present more severe symptoms and difficulties in treatment. In addition, persistent insomnia is the most common residual symptom in depressed patients and is considered a vital predictor of depression relapse and may contribute to unpleasant clinical outcomes (Hinkelmann et al., 20120. Questions involving feelings of hopelessness and suicidal ideations with or without a plan relate to issues of patient safety. Across psychiatric disorders, hopelessness is associated with suicidal ideation and behavior. A meta-analysis of 166 longitudinal studies (sample size not reported) found that hopelessness was associated with an increased risk of ideation (Ribeiro, Huang, Fox, & Franklin, 2018).
Family and social support system
Family and social support systems are imperative for any patient in recovery. If the patient is agreeable to discussions with family members, then a discussion with his wife would be helpful. Researc.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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.
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!
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
2. • Patients journey (apa saja hambatan pasien untuk bisa mendapatkan
pengobatan yang sesuai, terkecuali masalah harga)
• Implementasi guideline (apakah kita mengimplementasi guideline yang
ada, jika iya/tidak alasannya kenapa, guideline mana yang kita ikuti,
berapa banyak dokter yang mengikuti guideline)
• Apa saja tantangan/hambatan yang dijumpai dalam penerapan
guideline untuk tatalaksana AR ?
• Apa yang menjadi pertimbangan utama dalam menentukan tatalaksana
pasien AR ?
• Apakah nyeri yang berkurang atau membaik menjadi poin yang paling
utama dalam pencapaian goal of treatment di AR ?
Our topic
3. Rheumatoid arthritis (RA) is a systemic autoimmune disease
that causes joint inflammation and progressive erosion of
bone, leading to joint misalignment, loss of function, and
disability.
RA affects more 600.000 than million Indonesian adults.
Onset occurs most often between the ages of 30 and 50 years.
Women and older adults are more commonly affected.
Health Impact of Rheumatoid Arthritis
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at
www.effectivehealthcare.gov/dmardsra.cfm.
4. The goal of RA treatment is to:
Control pain & inflammation
Limit progressive damage
Reduce disease activity or induce remission
Maintain function
Treatment of Rheumatoid Arthritis
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
5. Disease-modifying anti-rheumatic drugs (DMARDs) interfere
with rheumatoid disease processes by blocking the production
or activity of the immune cells and their products that cause
inflammation and damage.
Treatment with DMARDs is increasing with the expectation that
they will lead to better disease control and more remissions.
Steroids—both low-dose systemic and intra-articular
formulations—are used as adjuncts to DMARD treatment.
DMARDs
6. Disease-modifying anti-rheumatic drugs (DMARDs) are in
common use for rheumatoid arthritis (RA), and several have
been approved by the U.S. Food and Drug Administration
for this indication.
DMARDs may be oral or biologic drugs.
The consensus of clinical experience has made
methotrexate, an oral DMARD, the first-line drug of choice
for treating RA.
DMARDs in Rheumatoid Arthritis Treatment (1 of 2)
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
7. Oral disease-modifying anti-rheumatic drugs (DMARDs) are small-
molecule chemical drugs.
The mechanism of action of each of these drugs is not well defined and is
unknown in some cases.
Biologic DMARDs block the activity of immunostimulatory
cytokines and other cell-signaling molecules.
Biologic DMARDs are genetically engineered antibodies and proteins.
Tumor necrosis factor-alpha blockers are the most typical members of
this drug class.
Other targets are interleukins 1 and 6 and the transmembrane proteins
CD20 and CD28.
DMARDs in Rheumatoid Arthritis Treatment (2 of 2)
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at
www.effectivehealthcare.gov/dmardsra.cfm.
8. Patients journey
• Apa saja hambatan pasien untuk bisa mendapatkan pengobatan yang
sesuai ?
• Keterlambatan diagnosis
• Keragaman pengetahuan dan kompetensi
• Akses ke fasilitas kesehatan yang tersedia KR
• Sistim rujukan
• Keterlambatan memulai DMARDs
• Pengetahuan dokter
• Ketersediaan DMARDs di faskes
• Kelemahan dalam follow up
• Timing
• Eskalasi
• Treat to target
9. Oral Disease-Modifying anti-rheumatic Drugs
Name Target of Activity
Hydroxychloroquine T-lymphocytes (?)
Leflunomide Pyridine synthesis
Methotrexate Dihydrofolate reductase; folate metabolism
Sulfasalazine Uncertain; multifactorial, including impairment of lymphocyte function and
cytokine synthesis
Oral DMARDs Included in the Comparative Effectiveness Review
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
10. Biologic DMARDs Included in the Comparative Effectiveness Review
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
Biologic Disease-Modifying anti-rheumatic Drugs
Name Trade Name Target of Activity
Adalimumab Humira® TNF-α
Certolizumab pegol Cimzia® TNF-α
Etanercept Enbrel® TNF-α
Golimumab Simponi® TNF-α
Infliximab Remicade® TNF-α
Abatacept Orencia® CD28
Anakinra Kineret® IL-1
Rituximab Rituxan® CD20
Tocilizumab Actemra®
RoActemra®
IL-6 receptor
Abbreviations: IL = interleukin; TNF-α = tumor necrosis factor-alpha
11. Implementasi guideline
• Apakah kita mengimplementasi guideline yang ada?
• Ya sebagian kecil
• Jika iya/tidak alasannya kenapa
• Akses terhadap update guideline
• Guideline mana yang kita ikuti
• IRA. EULAR, ACR, ARA ?, CRA ?
• Berapa banyak dokter yang mengikuti guideline?
• Belum ada survey.
• Rheumatologist umumnya sesuai
12. EULAR RECOMMENDATION FOR THE
MANAGEMENT OF RA
(Phase 1)
Smolen JS, et al. Ann Rheum Dis 2013;0:1-18
13. EULAR RECOMMENDATION FOR THE
MANAGEMENT OF RA
(Phase 2)
Smolen JS, et al. Ann Rheum Dis 2013;0:1-18
14. EULAR RECOMMENDATION FOR THE
MANAGEMENT OF RA
(Phase 3)
Smolen JS, et al. Ann Rheum Dis 2013;0:1-18
16. Tantangan
• Hambatan yang dijumpai dalam penerapan guideline
untuk tatalaksana AR ?
• Ketersediaan guideline
• Aksesibilitas
• Ketersediaan obat yang dianjurkandalam guideline
17. Apa yang menjadi pertimbangan utama dalam
menentukan tatalaksana pasien AR ?
• Kondisi pasien :
• Disease activity
• Disease damage
• Comorbidity
• Aspek DMARDs
• Efficacy, safety profile, drug interaction
• Ketersediaan obat dalam formularium:
• FORNAS
• Formularium Rumah Sakit
• Dukungan finansial / insurance
18. The strength of evidence for each of the following findings is low:
Patients with moderate rheumatoid arthritis (RA) had better overall
improvement and better functional status than patients with severe RA.
However, patients with severe RA had the greatest degree of
improvement from baseline.
In treatment with methotrexate (MTX), as the age of patients increased,
the likelihood of major clinical improvement decreased slightly; however,
overall age did not affect efficacy or risk of adverse effects.
Patient Characteristics on Outcomes of DMARD Treatment
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at
www.effectivehealthcare.gov/dmardsra.cfm.
19. Biologics showed no apparent influence on the risk of cardiovascular
events in the elderly (≥65 years of age).
Toxicity of MTX was more likely in patients with greater renal impairment.
High-risk comorbidities (cardiovascular disease, diabetes, malignancies,
and renal impairment) did not increase the risk of serious adverse events
or infections in patients treated with b-DMARDs.
Concomitant antidiabetic, antihypertensive, or statin medications given
to patients treated with b-DMARDs did not increase the risk of adverse
events.
20. Head-to-Head Comparisons of Oral DMARDs for Rheumatoid Arthritis
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
Comparison
N Studies; Patients
Reduced Symptoms or
Disease Activity
Limiting Radiographic
Progression Improved Function
Improved Quality of
Life
SSZ vs. MTX*
3; 1,001
(disease duration <3
years)
NSD (DAS)
SOE = Moderate
NSD
SOE = Moderate
NSD
(3 RCTs; 479 patients)
SOE = Moderate
NR
LEF vs. MTX*
2; 1,481
NSD (ACR20 rates)
SOE = Low
NSD
SOE = Low
Greater improvement with
LEF at 12 months (HAQ) but
less than the MCID
SOE = Low
Greater with LEF at 12
months
(SF-36 physical
component )
SOE = Low
LEF vs. SSZ
1; 358
SOE = Insufficient
NSD
SOE = Low
Greater improvement with
LEF (HAQ) to 24 months
SOE =Low
NR
*Methotrexate was used at 7.5 to 25 mg per week in the reported studies.
ACR20 = American College of Rheumatology 20-percent improvement criteria; DAS = disease activity score; HAQ = Health Assessment Questionnaire; LEF =
leflunomide; MCID = minimum clinically important difference; MTX = methotrexate;
NR = not reported; NSD = no statistically significant difference; RCT = randomized controlled trial; SOE = strength of evidence; SSZ = sulfasalazine
21. Head-to-Head Comparisons of Combination Treatment With Oral DMARDs
Intervention
N Studies;
Patients Comparator
Patient
Characteristics
Reduced Symptoms
or Disease Activity
Limiting
Radiographic
Progression Improved Function‡
SSZ plus
MTX*
4; 709
SSZ or MTX*
monotherapy
DMARD-naïve,
early RA†
NSD
SOE = Moderate
NSD
SOE = Moderate
NSD
SOE = Moderate
2 or 3 oral
DMARDs in
combination
(MTX*, SSZ,
HCQ)
2; 273
1 or 2 oral
DMARDs
Patients with
longstanding
active RA
3 oral DMARDs are
favored over 2 to
improve disease
activity.
SOE = Moderate
NR
Difference less than
MCID
SOE = Moderate
* Methotrexate was used at 7.5 to 25mg per week in the reported studies.
† Early rheumatoid arthritis is defined as <3 years.
‡ Health-related quality of life was not reported.
DMARD = disease-modifying anti-rheumatic drug; HCQ = hydroxychloroquine; LEF = leflunomide;
MCID = minimum clinically important difference; MTX = methotrexate; NR = not reported; NSD = no statistically significant
difference; RA = rheumatoid arthritis; SOE = strength of evidence; SSZ = sulfasalazine
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
22. Head-to-Head Comparisons of Biologic DMARDs
In patients with active RA (>3 years), with failed or inadequate disease response to DMARDs who did not receive an
anti–TNF-α DMARD, head-to-head comparisons of DMARDs produced the following results:
Intervention Comparator
Symptoms or
Disease Activity*
(N Studies; N Patients)
Function
(N Studies; N Patients)
Quality of Life
(N Studies; N Patients)
Etanercept Infliximab
Faster response with etanercept, but
NSD in the longer term
(6; 5,883) SOE = Low
2 of 3 studies reported NSD
(3; 2,239) Insufficient
Insufficient
Etanercept Adalimumab
ACR70 at 6 months showed NSD
(1; 2,326) SOE = Low
NSD
(1; 707) SOE = Low
NSD
(1; 707) SOE = Low
Adalimumab Infliximab
Symptom response (ACR20 at 6
months) and DAS at 1 year greater
with adalimumab
(2; 3,033) SOE = Low
Greater improvement at 12
months with adalimumab but
not greater than the MCID
(1; 707) SOE = Low
SF-36 physical component at 12
months favors adalimumab
(1; 707) SOE = Insufficient
Abatacept Infliximab
Greater decrease in DAS and greater
remission rate, both at 1 year, with
abatacept.
(3; 3,464) SOE = Low
NSD at 1 year
(1; 431) SOE = Low
SF-36 physical component at 1 year
favors abatacept but not greater
than the MCID
(1; 431) SOE = Low
*Radiographic progression not reported.
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
23. Head-to-Head Comparisons of Oral and Biologic DMARDs
Intervention
(N Studies,
N Patients) Comparator Symptoms or Disease Activity
Radiographic
Evidence of
Progression Functional Capacity
In patients with longstanding active RA who required a change in therapy*:
Biologic DMARDs
as a class
Oral DMARDs
as a class Higher chance of remission with biologics
than with oral DMARDs
SOE = Moderate
NR Insufficient
1 retrospective cohort study
N = 1,083
Biologic DMARDs Oral DMARDs
Higher response rates for biologic DMARDs
SOE = Moderate
NR Insufficient
4 RCTs, 2 cohort studies
N = 3,696
* Health-related quality of life was not reported.
DMARD = disease-modifying anti-rheumatic drug; NR = not reported; RA = rheumatoid arthritis; RCT = randomized controlled trial; SOE = strength of evidence
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
24. DMARD Combinations Versus Monotherapies
Intervention* Comparator
Symptoms or
Disease Activity
(N Studies;
N Participants)
Radiographic
Progression
(N Studies;
N Participants)
Function
(N Studies;
N Participants)
Quality of Life
(N Studies;
N Participants)
Biologic
DMARD plus
MTX†
Biologic
DMARD
Monotherapy
(5 RCT, 4 cohort; 9,804)
Combination is
more effective
SOE = Moderate
(2; 1, 495)
Less change with a
combination
SOE = Moderate
(2; 1,495)
Combination
treatment is more
effective
SOE = Moderate
(2; 1,495)
Combination
treatment is more
effective.
SOE = Low
Biologic
DMARD plus
MTX or SSZ
MTX† or SSZ
Monotherapy
(7; 4,482)
Combination is
more effective
SOE = High
(7; 4,482)
Less change with
combination
SOE = Moderate
(7 RCT, 1 cohort; 7,516)
Combination
treatment is more
effective
SOE = High
(7 RCT, 1 cohort;
7, 516)
Combination
treatment is more
effective
SOE = Moderate
* Patients with active disease whose disease did not respond to an oral DMARD did not benefit from including that oral
DMARD in combination with a biologic DMARD.
† MTX was used at a dose of 7.5 to 25mg per week in the reported studies.
In patients with longstanding active rheumatoid arthritis with inadequate disease control, head-to-head comparisons of
combined DMARDs and DMARD monotherapy were conducted.
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
25. DMARD Combinations Versus Monotherapies
In patients with early rheumatoid arthritis who had not been treated with methotrexate (MTX), or who had
not received MTX in the previous 3 months, head–to–head comparisons of combination therapy and MTX
monotherapy were examined for effects on function and quality of life.
Intervention Comparator Patient Characteristics
Function
(N Studies;
N Participants)
Quality of Life
(N Studies;
N Participants)
Biologic DMARD
plus MTX*
MTX* monotherapy
Early RA†
MTX Naïve or not recently
on MTX*
(2; 1,495)
Combination is more
effective.
SOE = Moderate
(2; 1,495)
Combination is more
effective.
SOE = Low
* Methotrexate was used at 7.5 to 25mg per week in the reported studies.
† Early RA is defined as disease of as less than 3 years’ duration.
DMARD = disease-modifying anti-rheumatic drug; MTX = methotrexate; RA = rheumatoid arthritis; SOE = strength of evidence
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
26. Comparative Benefits of Oral and Biologic DMARDs in Early RA
Patient Characteristics Intervention Comparator
Reduced Symptoms or
Disease Activity
Limiting
Radiographic
Progression Improved Function
Patients with early
RA*
2 to 3 oral DMARDs
plus corticosteroids
Oral DMARD
Monotherapy
Combination is more
effective at 28 but not 52
weeks.
(2; 354) SOE = Low
Combination is more
effective
(2; 354)
SOE = Low
Combination is
more effective† (2;
354)
SOE = Low
MTX-naïve patients
with aggressive early
RA
MTX‡ Adalimumab,
Etanercept
Results are similar
(2; 1,431)
SOE = Moderate
Biologic DMARD is
more effective at
limiting progression.
(2; 1,431)
SOE = Low
Results are similar
with MTX and
adalimumab§
(2; 1,431)
SOE = Low
MTX-naïve patients
with aggressive early
RA
MTX‡ plus biologic
DMARD
Biologic DMARD
Monotherapy
Combination is more
effective
(also improves remission
rates)
(1; 799) SOE = Low
Combination is more
effective.
(1; 799)
SOE = Low
NR§
* Early RA is disease of less than 3 years’ duration.
† Combination treatment is also more effective at improving quality of life.
‡ Methotrexate was used at a dose of 7.5 to 25mg per week in the reported studies.
§ Quality-of-life outcomes were not reported.
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
27. Combining methotrexate (MTX) or other oral disease-modifying anti-
rheumatic drugs (DMARDs) with a biologic DMARD does not alter the
adverse event rate found with the biologic DMARD alone.
Strength of Evidence = Low
Combining MTX and biologic DMARDs demonstrates a better
tolerability profile than MTX alone.
Strength of Evidence = Low
Evidence is insufficient to estimate differences in rates of specific
adverse events between the biologic and oral DMARDs.
Comparative Adverse Effects of Combining DMARDs
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
28. Withdrawal due to adverse events
Time to withdrawal
Infusion and injection-site reactions
Infections
Malignancy
Mortality
Cardiovascular and cerebrovascular events
Rare but serious adverse events: demyelination,
autoimmunity, pancytopenia, and hepatotoxicity
Adverse Effects of Interest in the Comparative Effectiveness Review
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
29. Apakah nyeri yang berkurang atau membaik menjadi poin yang
paling utama dalam pencapaian goal of treatment di AR ?
• Dari sisi pasien jawabannya: YA
• NYERI merupakan KELUHAN UTAMA disamping STIFFNESS pada pasien
dengan RA
• Dari sisi dokter : disease control
• Disease activity (inflammation)
• Function
• Disease damage
30. The natural history of rheumatoid arthritis (RA) and the role of
disease-modifying anti-rheumatic drugs (DMARDs) in reducing
symptoms and improving disease control
The potential benefits and adverse effects of DMARDs
Changes in lifestyle that can help relieve RA symptoms, such as
diet and exercise
Patient and family preferences and values regarding treatment
What To Discuss With Your Patients and Their Family
Donahue KE, Jonas D, Hansen RA, et al. Comparative Effectiveness Review No. 55. Available at www.effectivehealthcare.gov/dmardsra.cfm.
31. How to monitor Tt in RA?
• Disease activity is assessed by several parameters…
• Duration of morning stiffness
• Tender joints count
• Swollen joints count
• Observer global assessment
• Patient global assessment
• Visual analogue scale for pain
• Health assessment questionnaire
• ESR
• NSAID pill count etc
• Patient on MTX, SSZ or leflunamide show clinical improvement in 6-8 wks.
• Patient should be observed for 6 months before declaring a DMARD ineffective.
32. How long should Tt. be continued?
• Once remission is achieved , maintenance dose for long period is recommended.
• Relapse occurs in 3-5 months (1-2 months in case of MTX) if drug is discontinued
in most instances.
• DMARDs are discontinued by patients because of toxicity or secondary
failure(common after 1-2 yrs) and such patients might have to shift over different
DMARDs over 5-10 yrs.
• Disease flare may require escalation of DMARD dose with short course of
steroids.
Health Impact of Rheumatoid Arthritis
Rheumatoid arthritis (RA) is an autoimmune disease that causes joint inflammation and progressive erosion of bone, leading to joint misalignment, loss of function, and disability.
RA affects 1.3 million American adults. Onset occurs most often between the ages of 30 and 50 years. Women and older adults are more commonly affected.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International―University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Treatment of Rheumatoid Arthritis
The goal of RA treatment is to control pain, control inflammation, limit progressive damage, and reduce disease activity or induce remission.
Disease-modifying anti-rheumatic drugs (DMARDs) interfere with rheumatoid disease processes by blocking the production or activity of the immune cells and their products that cause inflammation and damage. Treatment with DMARDs is increasing with the expectation that they will lead to better disease control and more remissions. Corticosteroids—both low-dose systemic and intra-articular formulations—are used as adjuncts to DMARD treatment.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
DMARDs in Rheumatoid Arthritis Treatment (1 of 2)
Disease-modifying anti-rheumatic drugs (DMARDs) are in common use for rheumatoid arthritis (RA), and several have been approved by the U.S. Food and Drug Administration for this indication. DMARDs may be oral or biologic drugs.
The consensus of clinical experience has made methotrexate, a oral DMARD, the first-line drug of choice for treating RA.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
DMARDs in Rheumatoid Arthritis Treatment (2 of 2)
Oral disease-modifying anti-rheumatic drugs (DMARDs) are small-molecule chemical drugs. The mechanism of action of each of these drugs is not well defined and is unknown in some cases.
Biologic DMARDs block the activity of immunostimulatory cytokines and other cell-signaling molecules. They include genetically engineered antibodies and proteins. Tumor necrosis factor-alpha blockers are the most typical members of this drug class. Other targets are interleukins 1 and 6 and the transmembrane proteins CD20 and CD28.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Oral DMARDs Included in the Comparative Effectiveness Review
The oral disease-modifying anti-rheumatic drugs that have been studied for treatment of rheumatoid arthritis and were included in the comparative effectiveness review are:
Hydroxychloroquine: Its target of activity is uncertain but likely is T-lymphocytes.
Leflunomide: Its target of activity is pyridine synthesis.
Methotrexate: Its target of activity is dihydrofolate reductase and folate metabolism.
Sulfasalazine: Its target of activity is uncertain but may be multifactorial, including impairment of lymphocyte function and cytokine synthesis.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Biologic DMARDs Included in the Comparative Effectiveness Review
The biologic disease-modifying anti-rheumatic drugs (DMARDs) that have been studied for treatment of rheumatoid arthritis and were included in the comparative effectiveness review are:
The biologic DMARDs that target tumor necrosis factor-alpha (TNF-α) include adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), and infliximab (Remicade).
Other biologic DMARDs included in the review target immune system components other than TNF-α. They are:
Abatacept (Orencia): Its target of activity is CD28.
Anakinra (Kineret): Its target of activity is interleukin 1.
Rituximab (Rituxan): Its target of activity is CD20.
Tocilizumab (Actemra, RoActemra): Its target of activity is the interleukin-6 receptor.
Reference:Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Other Findings: Influence of Patient Characteristics on Outcomes of DMARD Treatment
The strength of evidence for each of the following findings is low:
- Patients with moderate rheumatoid arthritis (RA) had better overall improvement and better functional status than patients with severe RA. However, patients with severe RA had the greatest degree of improvement from baseline.
- In treatment with methotrexate (MTX), as the age of patients increased, the likelihood of major clinical improvement decreased slightly; however, overall age did not affect efficacy or risk of adverse effects.
- Biologics showed no apparent influence on the risk of cardiovascular events in the elderly (≥65 years of age).
- Toxicity of MTX was more likely in patients with greater renal impairment.
- High-risk comorbidities (cardiovascular disease, diabetes, malignancies, and renal impairment) did not increase the risk of serious adverse events or infections in patients treated with anakinra.
- Concomitant antidiabetic, antihypertensive, or statin medications given to patients treated with anakinra did not increase the risk of adverse events.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Summary of Results: Head-to-Head Comparisons of Oral DMARDs for Rheumatoid Arthritis
Studies of oral disease-modifying anti-rheumatic drugs (DMARDs) include head-to head-comparisons, but the number of studies and patients examined is limited and the strength of evidence in support of the findings is low or moderate. For some outcomes, the evidence is insufficient for a conclusion or the outcomes were not studied.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Summary of Results: Head-to-head Comparisons of Combination Treatment With Oral DMARDs
Studies of oral disease-modifying anti-rheumatic drugs (DMARDs) include head-to-head comparisons of DMARDs used in combination and compared with monotherapy or other DMARD combinations. Patient populations included those with early rheumatoid arthritis who had not been treated with DMARDs, and those patients with longstanding active rheumatoid arthritis and inadequate response to treatment. The number of studies and patients examined is limited, but where available, the strength of evidence in support of the findings is moderate. Some outcomes were not reported in all studies.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Summary of Results: Head-to-Head Comparisons of Biologic DMARDs
Head-to-head comparisons of biologic DMARDs were evaluated for the effectiveness review. Patient populations in the included studies were patients with active RA for longer than 3 years whose disease not did respond or inadequately responded to DMARDs but had not previously treated with an anti–TNF-α DMARD. This table presents a summary of the results of those studies, organized according to the interventions compared in each study. Disease activity and symptom response, functional status, and quality-of-life outcomes were reported. Radiographic evidence of progression was not reported in the studies. The evidence is limited for all comparisons; thus, the strength of evidence is low or insufficient.
Abbreviations:
ACR70 = American College of Rheumatology 70-percent improvement criteria; ACR20 = American College of Rheumatology 20-percent improvement criteria; DAS = Disease Activity Score; DMARD = disease-modifying anti-rheumatic drug; MCID = minimum clinically important difference; NSD = no statistically significant difference; RA = rheumatoid arthritis; SOE = strength of evidence; TNF-α = tumor necrosis factor-alpha
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Summary of Results: Head-to-Head Comparisons of Oral and Biologic DMARDs
The reviewed studies included direct comparisons of oral and biologic disease-modifying anti-rheumatic drugs (DMARDs) used to treat patients with longstanding active rheumatoid arthritis who required a change in therapy. A retrospective cohort study of 1,083 patients found that as a class, biologic DMARDs resulted in more remissions when compared with oral DMARDs as a class. The systematic review found that biologic DMARDs achieved a higher response rate than oral DMARDs. The strength of evidence for this finding is moderate.
Four randomized controlled trials and two retrospective cohort studies evaluated 3,696 patients in comparisons of biologic DMARDs with oral DMARDs. Higher symptom response rates were found with biologic DMARDs. The strength of the evidence for this conclusion is moderate.
Radiographic evidence of progression was not reported in the studies presented here, and evidence for findings of effect on functional capacity was insufficient to permit conclusions.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Summary of Results: DMARD Combinations Versus Monotherapies
In patients with longstanding active rheumatoid arthritis with inadequate disease control, head-to-head comparisons were made of combined DMARDs and DMARD monotherapy. Overall, combination treatment with biologic DMARDs and an oral DMARD is more effective than either used as monotherapy. Disease activity, radiographic progression, functional status, and quality of life all are greater improved with the combination therapy. The strength of evidence for these findings varies among the specific outcomes, with most supported by moderate or high strength of evidence.
Abbreviations:
DMARD = disease-modifying anti-rheumatic drug; MTX = methotrexate; RA = rheumatoid arthritis; RCT = randomized controlled trial; SOE = strength of evidence; SSZ = sulfasalazine
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Summary of Results: DMARD Combinations Versus Monotherapies
In patients with early rheumatoid arthritis who had not been treated with methotrexate (MTX), or who had not received MTX in the previous 3 months, head–to–head comparisons of combination therapy and MTX monotherapy were examined for effects on function and quality of life. Combination therapy was more effective in achieving improvements in function and quality of life. The strength of evidence is moderate for functional status and low for quality of life.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Summary of Results: Comparative Benefits of DMARDs for Patients With Early RA
Some clinical research has focused on treatment of patients with early rheumatoid arthritis, defined for this comparative effectiveness review as less than 3 years’ duration of disease. This table presents a summary of the results of those studies, organized according to the patient characteristics and by the interventions compared in the study. Disease activity and symptom response, radiographic evidence of progression, and functional status were reported. Quality-of-life outcomes were not reported in the studies. The strength of evidence is moderate for one conclusion, finding that methotrexate and adalimumab or etanercept produce similar effects on symptoms. The evidence is limited for all other comparisons, making the strength of evidence low.
Abbreviations:
DMARD = disease-modifying anti-rheumatic drug; MTX = methotrexate; NR = not reported; RA = rheumatoid arthritis; SOE = strength of evidence
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Comparative Adverse Effects of Combining DMARDs
Combining methotrexate (MTX) or other oral disease-modifying anti-rheumatic drugs (DMARDs) with a biologic DMARD does not alter the adverse event rate found with the biologic DMARD alone. The strength of evidence for this finding is low.
Combining MTX and biologic DMARDs demonstrates a better tolerability profile than MTX alone. The strength of evidence for this finding is low.
Evidence is insufficient to estimate differences in rates of specific adverse events between the biologic and oral DMARDs.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
Adverse Effects of Interest in the Comparative Effectiveness Review
For analysis of the clinical study evidence, reviewers focused on these adverse effects measurements:
- Withdrawal due to adverse events
- Time to withdrawal
- Infusion and injection-site reactions
- Infections
- Malignancy
- Mortality
- Cardiovascular and cerebrovascular events
- Rare but serious adverse events: demyelination, autoimmunity, pancytopenia, and hepatotoxicity
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.
What To Discuss With Your Patients and Their Caregivers
In discussions with patients who have rheumatoid arthritis (RA) and their caregivers, topics related to the comparative effectiveness review evidence include the natural history of RA, the role of disease-modifying anti-rheumatic drugs (DMARDs) in reducing symptoms and improving disease control, the potential benefits and adverse effects of DMARDs, changes in lifestyle that can help relieve symptoms (e.g., diet and exercise), and patient and caregiver preferences and values regarding treatment.
Reference:
Donahue KE, Jonas D, Hansen RA, et al. Drug Therapy for Rheumatoid Arthritis in Adults: An Update. Comparative Effectiveness Review No. 55 (Prepared by the RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; April 2012. AHRQ Publication No. 12-EHC025-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsra.cfm.