Unbranded Rheumatoid Arthritis Booklet

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Unbranded Rheumatoid Arthritis Booklet written for BMS while working at Corbett Accel.

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Unbranded Rheumatoid Arthritis Booklet

  1. 1. Managing rheumatoid arthritis Seize the moment e pl m sa g in rit iw sk w ko cz Ka al st ry C © 2005 Bristol-Myers Squibb Company B5-D0003 5/05 Printed in USA Discovering the Next Future™ Discovering the Next Future™
  2. 2. Establishing Diagnosis Diagnosis of RA can be difficult, particularly in the Considering the average delay before an RA patient early stages of the disease.1 Patients will often first receives treatment, it is imperative for a physician, self-treat their symptoms before seeing a general especially a rheumatologist, to diagnose RA as early practitioner (GP). Considering the subjective as possible and initiate the appropriate treatment in nature of RA symptoms, many GPs have difficulty order to potentially reduce disease progression.7 determining the etiology of the patient’s complaints Initial Evaluation due to their limited experience in diagnosis and The initial RA patient evaluation may incorporate management. Difficulties such as these may delay both objective and subjective measures including1: the correct diagnosis of RA and subsequent treatment.3,4 According to one thought leader, the median time I physical examination to diagnosis of early RA is 18 weeks.4 Only 6% to I laboratory tests 14% of GPs refer patients to a rheumatologist within I radiography 6 weeks. Most GPs refer new arthritic patients to a e I duration and degree of joint pain, morning rheumatologist within 3 months, but many wait to pl m stiffness, and fatigue refer patients from 3 to 6 months.5 Thus, the sa g majority of patients appear to be waiting longer I actively inflamed joints (eg, synovitis) in rit than they should for treatment, even though 70% iw I functional status of RA cases can be diagnosed by a rheumatologist sk w I mechanical joint problems within 2 weeks of the first visit.4 The American ko cz I extraarticular disease College of Rheumatology (ACR) guidelines state that Ka the majority of newly diagnosed patients should be al st Comorbidities and other assessments of active RA started on DMARDs within 3 months of diagnosis.1 ry C damage should also be documented. Baseline data can be collected regarding quality of life (QOL), patients’ and physicians’ pain assessments of disease RA treatment is often delayed activity using visual analog scales (VAS), or other validated QOL measurement tools.1 There is growing I Many patients wait >3 months from evidence that these QOL measures, such as the symptom onset to first GP appointment6 Stanford Health Assessment Questionnaire (HAQ), I Many patients wait >3 months for a are correlated with underlying structural damage specialist referral6 and long-term reduction in functional ability.8,9 I Only 6% to 14% of GPs refer patients to A baseline laboratory assessment should include a rheumatologist within 6 weeks5 a complete blood cell count with white blood cell I DMARD therapy delayed even after seeing differential and platelet counts; measurement of a specialist6 erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP); and measurement of rheumatoid factor (RF). Hepatic and renal function should be 3
  3. 3. evaluated since many antirheumatic agents can cause is now widely accepted that aggressive treatment Ongoing Assessment Baseline evaluation of disease toxicity problems and would be contraindicated if should be initiated as soon as diagnosis is made of Disease Activity activity and damage 1 organs are impaired.1 since numerous studies have concluded that DMARDs can inhibit disease progression in patients with early Subjective The physician should assess whether the patient’s Radiographs of the hands, feet, and other affected RA. For those patients with unfavorable prognostic I Degree of joint pain disease is active or inactive at each follow-up visit. joints should be used to establish a baseline for future factors, early DMARD treatment should be initiated I Duration of morning stiffness Symptoms of active disease, functional status, assessment of structural damage.1 immediately upon diagnosis.1 I Duration of fatigue mechanical joint problems, presence of extraarticular I Limitation of function disease, and radiographic damage should be Estimating Prognosis Baseline assessment of disease activity documented.1 A patient’s prognosis is closely related to disease activity Physical Examination at onset since it has been shown that persistent Creating a plan for treatment requires an estimate I Actively inflamed joints Symptoms of inflammation including prolonged inflammation of the joint leads to joint destruction.7 of prognosis. Earlier age of disease onset, elevated (tender and swollen joint counts) morning stiffness, fatigue, and active synovitis on ESR, high titer of RF, and swelling of 20 or more I Mechanical joint problems: loss of motion, joint examination indicate active disease and may e In early RA, analysis of the feet is critical since damage joints are associated with a poorer prognosis. Other pl crepitus, instability, malalignment, necessitate treatment modifications. Because the m usually occurs there first.10 A consistent predictor of factors that may be related to poor prognosis sa and/or deformity examination of joints may not always adequately g later damage is the radiological score of the feet include: extraarticular manifestations of RA (eg, I Extraarticular manifestations in gauge disease activity, periodic assessments of rit and/or hands in the first 3 years of disease.11,12 rheumatoid nodules), Sjögren’s syndrome, episcleritis iw functional status, ESR or CRP measurement, sk However, not all patients have and scleritis, interstitial Laboratory and radiography should also be made.1 w radiographic evidence of structual lung disease, systemic ko I Erythrocyte sedimentation rate/C-reactive cz damage in the first year.11 vasculitis, pericardial protein level Ka Functional status may be assessed by a questionnaire involvement, and al I Rheumatoid factor such as the HAQ. The HAQ is an indicator of disease st Felty’s syndrome.1 Predictive models to determine ry I Complete blood cell count outcome and severity. It is important to determine C progressive disease have been I Electrolyte levels whether a functional decline is due to inflammation, developed based on some of the Studies have demonstrated I Creatinine level mechanical damage, or both. Strategies for prognostic markers discussed in that patients with active I Hepatic enzyme levels (AST, ALT, and albumin) treatment will differ according to the cause the previous section12,13; however, polyarticular, RF-positive I Urinalysis of the functional decline.1 there is a need for validation of RA have more than a 70% I Synovial fluid analysis these models in early and chance of developing I Stool guaiac While the ACR response criteria and the disease persistent RA.10 structural damage (joint activity score (DAS) are routinely used in clinical trials damage or erosions) within Other to measure efficacy, these scales should not be used 2 years. Because of this, it I Functional status or quality of life assessments as the only measure to monitor an individual using standardized questionnaires patient’s clinical response. A combination of clinical I Physician’s Global Assessment of Disease Activity I Patient’s Global Assessment of Disease Activity Radiography Radiographs are an important tool in establishing a I Radiographs of selected involved joints diagnosis of RA and estimating baseline disease activity/joint damage. Disease progression can be monitored with subsequent x-rays. 4 5
  4. 4. judgment and quantitative measures should be used I RF (positivity and titer) erosions. Those patients with two RA-associated alleles New Imaging Techniques for 6p25.3— 6p25.2— in addition to other validated measures such as1: (DRB1*04 or DRB1*01) have demonstrated more I radiographic scores within Diagnoses and Prediction 6p25.1— 6p24.3— radiographic erosions and joint replacement the first year of disease onset 6p24.2— of Outcomes compared with patients without these alleles.13,16 6p24.1— I VAS I HAQ 6p23— I scales of global response or pain by 6p22.3— I CRP or ESR Immunological factors Efficient methods for diagnosing, estimating the patient 6p22.2— Rheumatoid factor prognosis, and monitoring disease progression are I the presence of HLA-DRB1*04 6p22.1— I scales of global response by the physician As immunological markers go, RF has received the essential in RA. Magnetic resonance imaging (MRI) HLA- 6p21.33— shared epitope (SE) alleles10,11 DRB1 gene 6p21.32— I joint tenderness and/or swelling most attention for use in predicting prognosis.10 and musculoskeletal ultrasonography (MUS) are (ie, any of the alternative 6p21.31— There is evidence that in early RA, RF is associated imaging techniques that are playing an increasingly forms of a gene that may I laboratory data 6p21.2— with a more severe radiological outcome.13,17-19 Some valuable role in the assessment of patients with occur at a given locus) 6p21.1— studies suggest that a positive test for RF or a high RF inflammatory diseases. These tools are now These measures should be followed in each patient titer at baseline is indicative of poor outcome in early routinely used in many early arthritis clinics Genetic factors to gauge improvement. In addition to monitoring 6p12.3— e RA. Another study has demonstrated the validity of in the evaluation of joint, tendon, and soft tissue Several genes have been disease activity and progression, a patient’s pl 6p12.2— m 6p12.1— RF positivity at 1 year.20 By and large, the literature inflammation and bone damage. Their ability examined in RA, but HLA-DRB1* tolerance of adverse events (or side effects) and sa 6p11.2— suggests that a positive IgM RF at disease onset 6p11.1— to visualize, quantify, and characterize the earliest g are the only genes that have been concern of risks (such as infections) should be in 6q11.1— rit predicts high radiographic progression.10 inflammatory changes provides useful clinical 6q11.2— repeatedly associated with RA.10 addressed.14 Patients with an incomplete response iw 6q12— tools and contributes to an understanding of sk This is particularly true for or who are intolerant of their medication may need w Anticyclic citrullinated peptides 6q13— disease pathogenesis.23 HLA-DRB1 alleles with a similar ko a different treatment plan.15 cz The most specific marker for RA is anticyclic 6q14.1— amino acid sequence referred to Ka 6q14.2— citrullinated peptides (anti-CCP); however, this For assessment of joint damage, x-ray is the traditional Biomarkers that assess ongoing as the shared epitope. Among al 6q14.3— st marker has not been routinely used in practice.10 disease activity gold standard.24 However, conventional radiographs alleles examined, HLA-DRB1*0401 ry 6q15— C Thus, there is a limited amount of literature limit visualization of the joint and do not allow With the advent of new treatment strategies and and DRB1*0404 have been evaluating anti-CCP as a tool for prognosis. 6q16.1— assessment of changes in joint tissues that can therapeutic options, there is a need for a predictive associated with radiographic Longitudinal studies in early arthritis cohorts 6q16.2— precede joint damage by months or years.25,26 model for use in clinical practice in order to design 6q16.3— have demonstrated, however, that the presence A preliminary study comparing conventional the most appropriate therapeutic strategy for patients of anti-CCP at baseline is a good predictor of radiograph, MRI, ultrasound, and computerized in early and persistent RA. The ideal prognostic index 6q21— radiographic joint damage in follow-up periods tomography assessed erosions of the humeral would include reliable markers such as10: of 5 to 6 years.21,22 head in patients with RA. MRI, ultrasound, and 6q22.1— 6q22.2— computerized tomography were all more sensitive 6q22.31— than conventional radiograph at detecting bone 6q22.32— erosions. Furthermore, MRI and ultrasound were 6q22.33— better than computerized tomography at detecting small erosions.27 Computerized tomography emits 6q23.1— 6q23.2— 6q23.3— 6q24.1— 6q24.2— 6q24.3— Gene map of chromosome 6 showing the location of the HLA-DRB1 gene that has 6q25.1— been associated with RA. 6q25.2— 6q25.3— 6q26— 6q27— 6 7
  5. 5. MRI of a hand early in the RA disease process. Edema is apparent on the third and fourth metacarpophalangeal joints indicating inflammation and disease activity. Reproduced with permission from the Arthritis Research Campaign (www.arc.org.uk). ionizing radiation28 and its Ultrasound validation is required regarding the potential use of The advantages and disadvantages of sensitivity to detect small ultrasound in early RA.23 There are still very limited MRI and ultrasound35 Traditional MUS has been erosive changes is inferior to data regarding the diagnostic and prognostic value used for some time for MRI or MUS27,28; thus, it is rarely of ultrasound, as well as areas such as the monitoring detecting joint and soft Advantages Disadvantages used in clinical practice. of joint inflammation and destruction. Ultrasound tissue inflammation.32 It has is a more accessible, lower-in-cost, and patient-friendly also been described as the I Safe I Higher costs than MRI Magnetic resonance technology than MRI.35 In the near future, it may gold standard imaging radiography I No ionizing radiation imaging become a routinely used clinical tool for the technique for evaluating I Less availability than I No increased risk of rheumatologist.36 Magnetic resonance imaging of tendon involvement in radiography malignancies the joints has stimulated great rheumatic diseases.33 More I Longer examination I Allergic reactions to interest as a research tool.29 The Certainly, the fact that rheumatoid activity and recent MUS techniques, such time contrast agents main advantage of MRI is that it damage can be imaged and measured in new as Doppler, have shown are rare I Evaluation of only a allows 3-dimensional assessment ways using MRI and ultrasound opens a new frontier promise for assessing patients few joints per session e of a large number of anatomical in disease management for rheumatologists. with inflammation. Doppler pl I Time required to m structures in and around a joint.23 Opportunities for clinical practice include earlier is a technique that makes sa evaluate an MRI g The multiplanar properties of MRI and its ability and more accurate diagnoses and meticulous noninvasive measurements of blood flow. Power examination in rit to identify small cortical defects allow superior evaluation of therapeutic response. These Doppler is valuable for assessing low-velocity iw sensitivity to conventional radiography for techniques provide optimal opportunities for sk vascular flow in small vessels such as the I Physical limitations I Noninvasive Ultrasound w detecting bone erosions.23 MRI can assess osseous disease control.7,35 There are technical challenges, synovium. Therefore, it can measure and detect (ie, not all areas are ko I Relatively inexpensive cz accessible, thus whole changes and has the ability to visualize soft tissue however, with MRI and ultrasound, for instance, in changes in the vascularity of joints and soft tissue Ka I No ionizing radiation joint assessment is with high spatial resolution and good contrast.25,29 standardizing scoring systems.23,29,30,36,37 A thorough due to inflammation.32 A study in patients with al I Ability to visualize rarely possible) st validation of MRI findings as a substitute for inflammatory arthritis proposes that MUS may even ry both inflammatory C I Dependency on a radiographic outcome measures is required before have more sensitivity than MRI for the detection of The increased popularity of MRI is a result of better and destructive skilled operator routine use in clinical trials is recommended. But synovitis in finger joints.34 However, further access, reduction in cost, and developments in disease mechanisms I Poor objective these tools have a possible future in the diagnosis resolution, sequences, and I Easily repeated documentation and management of RA. software. It is contended that I Possibility of of findings these features make MRI an examining several ideal technique for detecting joints in 1 session the earliest pathological changes I Potential for being performed by associated with inflammatory rheumatologists in arthritis.23 Furthermore, there outpatient clinics is evidence that using MRI in I Potential for guiding patients with early RA can interventions A sonogram of the wrist assist in identifying those with produced by ultrasound can be used as a diagnostic tool for RA aggressive disease.30,31 and to monitor ongoing disease progression. 8 9
  6. 6. Treatment Goals From a physician’s perspective, goals central to the I risk factors Remission some suggestion that the standard primary treatment of RA include decreasing pain, preventing endpoint of RA clinical trials should be a response The notion of setting remission as a treatment goal I comorbid conditions loss of function, improving QOL, and inhibiting of ACR 70 or greater to more accurately indicate for RA is becoming more prominent within clinical I what drug monitoring is needed structural damage.1,38 While patients may benefit from treatment efficacy.9 settings.9 The challenge of introducing remission as I patient preferences the outcomes of these goals, they often rate the the standard goal of treatment lies in establishing a following symptoms as most important: functional I patient expectations of treatment In addition to the discussion over which accumulative universally accepted definition that can be easily ability, pain, cognition, gastrointestinal side effects, measurement should be used to indicate a state of assessed and is accurately quantified. It is essential I potential barriers to treatment recommendations fatigue, and sleep.39 Since RA is a complex, chronic remission, there is also debate over which core to define the point at which disease activity has Current therapeutic options allow physicians the autoimmune disease that is prone to periods of criteria most accurately reflect the degree of disease been stably reduced or repressed sufficiently. ability to treat RA patients at any stage of disease. increasing and decreasing severity, patient progression.8,9,43 Some experts argue that, although Furthermore, in order to set remission as a study Although early intervention is important, so is involvement in the development of a long-term swollen joint counts and tender joint counts are endpoint within a clinical trial, concise criteria that assessing the efficacy of treatment and controlling treatment plan is important for improving outcomes. important indicators of disease activity, only can be easily measured and provide reliable data disease long term for patients with more advanced Key opinion leaders recommend that physicians and radiographic analysis can provide objective evidence must be identified.8,40,42,43 disease or who are nonresponsive to therapy. e patients should first discuss treatment options. of joint degradation and true disease progression.8,9 pl m Discussions should revolve around1: Neither ACR nor DAS standards include radiographic Currently, there is much discussion on what constitutes sa While efficacy is critical for successful clinical g assessment in their core analytical criteria. Advocates remission in RA. For many years, major clinical I the patient’s prognosis and treatment options in rit outcomes, good tolerability is also important. Thus, of more advanced methods of visualizing disease studies had equated a response of ACR 70 or iw I associated costs both safety and tolerability should be monitored activity suggest that even more sensitive methods, sk greater40 and/or a DAS28 score less than 2.6 with w I possible adverse effects as patients progress on therapy. such as MRI, be utilized to better detect early erosions ko a state of remission.43 Another recently introduced cz I when the patient may expect a response and pre-erosive inflammation that cannot be seen measure is the major clinical response (MCR), in Ka on early radiographs.26 which a response of an ACR 70 or greater is al st maintained for at least 6 consecutive months.44 ry C Common definitions of remission in RA40,41 Achieving remission for more RA patients is becoming increasingly possible with the introduction of Previous studies have traditionally reserved responses ACR DAS28 DMARDs. With the reality of remission, however, of ACR 70 or DAS28 <2.6 as secondary endpoints, comes the necessity to identify the most accurate using ACR 20 and ACR 50 criteria as the primary 5 of the following for at least DAS28 <2.6 criteria for monitoring treatment efficacy and measurements to indicate clinical efficacy. Recent 2 months: DAS28 score calculated from: Definition measuring patient success so that remission can be statistics demonstrating an increased probability of I No fatigue I No tender joints I 28 tender joint counts targeted and measured as a new treatment goal. work disability in patients only achieving responses I No joint pain I No swollen joints I 28 swollen joint counts of ACR 20 or ACR 50, but never experiencing ACR 70, suggest that ACR 20 and ACR 50 are not I Normal ESR I Morning stiffness I Patient global assessment of <15 minutes disease activity adequate responses and, therefore, not reliably reflective of treatment efficacy. There has been I ESR or CRP Originally defined in 1981. These The DAS28 criteria for remission are criteria are still preliminary. The becoming widely used in today’s clinical Future ACR definition has been criticized trials. The DAS28 is considered to be less for being too stringent, since few patients restrictive than the ACR definition for achieve remission by these criteria. remission. 10 11
  7. 7. Treatment Options Pharmacological Options with RA immunopathology. However, DMARDs The guidelines for RA treatment are as follows1: have the ability to alter the disease through reduction or prevention of joint damage, and preservation of Since preventing loss of function, decreasing pain, I Establish diagnosis of RA early joint integrity and function.1 improving patient QOL, and inhibiting structural I Document baseline disease activity and damage I Estimate prognosis damage are central goals of treatment, drug therapy All RA patients are considered candidates for DMARD should be tailored to achieve these outcomes. In therapy. DMARD therapy should be initiated within addition, some things to be considered when Primary Care Physician 3 months in patients with confirmed diagnoses who selecting a medication include the ability to deliver Initiate therapy continue to have the following symptoms despite I Patient education an adequate response, the incidence and seriousness adequate NSAID treatment1: I Start DMARD(s) within 3 months of adverse events, and the likelihood of patient I Consider NSAID I ongoing joint pain compliance.1 Therapies that achieve an ideal balance I Consider local or low-dose systemic steroids of efficacy, safety, and tolerability deliver true I considerable morning stiffness or fatigue I Physical therapy/occupational therapy clinical effectiveness. I active synovitis e pl m I continuous elevation of ESR or CRP levels sa In order to achieve optimal patient outcomes, Rheumatologist g Periodically assess disease activity I radiographic joint damage in pharmacological therapy usually consists of a rit iw combination of NSAIDS, DMARDs, and/or steroids Any untreated patient with persistent synovitis and sk (corticosteroids).1 joint damage should be immediately started on w ko Inadequate DMARD treatment to prevent or slow further damage.1 cz Adequate response response (ie, ongoing Ka NSAIDs with decreased active disease after al disease activity These drugs reduce inflammation and have analgesic 3 months of Traditional st ry maximal therapy) properties, but they do not prevent joint destruction Traditional DMARDs have been used in RA therapy C or alter the disease course.1 to successfully reduce inflammation and associated symptoms.1,45 Change/Add DMARDs Steroids Corticosteroids work quickly to alleviate damaging Rheumatologists often select traditional DMARD MTX* naive Suboptimal MTX response and painful inflammation. They are associated with therapy initially, especially for patients with more MTX Other Combination Combination Other Biologics potential side effects like brittle bones, cataracts, and active disease.1 mono Rx Rx Rx mono Rx elevated blood sugar, especially if they are taken in Mono Rx Combination high doses or over the long term. Inflammation Biologic DMARDs Rx may be controlled in a few affected joints by Six years ago, if a patient had RA and did not injecting a corticosteroid compound directly respond to traditional DMARDs, there was little a Multiple DMARD failure into inflamed joint(s).38 rheumatologist could do. Today there is the option of biologic DMARDs. Symptomatic and/or DMARDs structural joint damage Although NSAIDs and corticosteroids may reduce inflammation and alleviate pain, they do not interfere Surgery *MTX = Methotrexate 12 13
  8. 8. Biologic DMARDs continued The use of traditional DMARDs and the introduction Nonpharmacological options flares and concomitant loss of function. Cognitive- Current guidelines recommend a combination of of the biologic DMARDs have begun to redefine behavioral programs that help patients take a greater Optimum treatment requires more than just drug NSAIDs, corticosteroids, and early introduction of both expectations for the effectiveness of RA therapies.1,47 role in their disease management can improve patient therapy. Sometimes, RA patients may require periods traditional and biologic DMARDs. The more recent DMARDs have allowed physicians to go beyond health and reduce health care utilization.1 of rest, job modification or time off from work, a availability of targeted therapeutics for the treatment of just treating symptoms and start inhibiting disease change of occupation, or termination of work RA has led to a significant difference in the ability to progression and joint destruction, while also The risks and benefits of existing treatment plans altogether. Patients will likely benefit from instruction inhibit disease progression and improve patient preserving joint function.1 should also be reviewed with the patient. The health in joint protection, energy conservation, and creation response and quality of life. Moreover, it has opened care team may use an interdisciplinary approach. of a home exercise program (joint range of motion the door for major advances in the treatment of RA Advances in biologic treatments for autoimmune Rheumatologists, primary care physicians, nurses, and and strength exercises).1 and led to more aggressive treatment guidelines.1 disease have set a new standard for RA therapy, and other health care staff members often play a significant elaborate research of immune pathways has led to a role in educating patients and their families about the Treatment starts with educating the patient about the more intricate understanding of RA immunopathology. The American College of Rheumatology’s most recent disease and how to offer long-term supportive care. disease. Patients will have to learn to live with RA and As a result, potential new therapeutic targets within position statement dictates that, when clinically Patients may find consultations with become involved in the treatment process e RA immunopathology, such as IL-6, B cells, and appropriate, all patients with serious rheumatic disease physical therapists, occupational decisions. Emotional difficulties may arise pl m T-cell activation, have been investigated. Hopefully, must have these biologic agents.46 therapists, patient educators, and if treatment does not fully control this sa g new alternatives will be identified to stop disease social workers beneficial.1,38 chronic disease. The patient should be in rit progression and prevent permanent disability while Although the genetically engineered biologic made aware that RA is associated with iw preserving patient immune response.47 sk DMARDs all work in different ways, they all w block proteins called cytokines, which contribute to ko cz Low-impact exercises such as pool inflammation.38 This development has been a major Ka therapy are beneficial for RA patients as advance in RA treatment. nonpharmacological treatment options. al st ry C Some of the most effective anticytokine drugs are antagonists to TNFα, which is a critical mediator of the RA inflammatory cascade. Clinical trials have shown these drugs improve clinical signs and symptoms, measured by ACR 20, 50, and/or 70 scores. These drugs have demonstrated efficacy in combination therapy with traditional DMARDs when administered to patients with ongoing active RA despite sufficient doses.1 14 15

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