复旦大学：《循证医学》课程教学资源（参考教材）Unit 08 生命质量的分析评价（主讲教师：姜林娣）.pdf

Pharmacoeconomics 2008; 26 (10): 831-846 REVIEW ARTICLE 1170-7690/08/0010-0831/$48.00/0 © 2008 Adis Data Information BV. All rights reserved. Quality-of-Life Assessment in Rheumatoid Arthritis Anthony S. Russell Rheumatic Disease Unit, Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada Contents Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 831 1. Quality of Life (QOL) in Patients with Rheumatoid Arthritis (RA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 832 2. Clinical Assessment of RA Disease Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 833 3. QOL Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 833 3.1 Generic Instruments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 833 3.2 Health Utilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 835 3.3 Disease-Specific Instruments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 836 4. Use of Assessment Instruments in Clinical Practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 836 5. Do Current Treatments Improve QOL in RA? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 837 5.1 Infliximab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 837 5.2 Adalimumab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 837 5.3 Etanercept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 838 5.4 Anakinra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 838 5.5 Rituximab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 839 5.6 Abatacept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 839 5.7 Summary of Health-Related QOL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 842 6. Economic Implications of QOL in RA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 842 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 844 Abstract Rheumatoid arthritis (RA) is a chronic and lifelong autoimmune disorder that results in significant pain, disability and excess mortality if untreated or inadequately treated. Quality-of-life (QOL) assessments are particularly important in the absence of a cure for RA. Generic and disease-specific patient-reported QOL instruments, such as the Health Assessment Questionnaire (HAQ) Disability Index and the SF-36, have proven validity and sensitivity for assessment of changes in QOL in clinical trials of disease-modifying anti-rheumatic drugs (DMARDs). However, these instruments are rarely utilized in clinical practice, and patients have reported that the actual clinical assessments alone do not address important parameters, such as fatigue and disturbed sleep, which significantly affect QOL. New biological DMARDs have shown significant efficacy in improving clinical and QOL parameters in randomized controlled trials. However, the high cost of biological DMARDs compared with non-biological DMARDs is a factor in the increasing health costs associated with the treatment of RA. Generic health utility instruments that measure QOL parameters enable calculation of the increased QALYs associated with more costly treatment in patients with RA. The costs per QALY associated with biological DMARDs in RA appear to be

832 Russell comparable to those of other accepted medical interventions. Interest in incorporating QOL parameters in formulary and public health decision making concerning the use of new agents for RA is increasing. 1. Quality of Life (QOL) in Patients with is decreasing because of rising healthcare costs.[4] Rheumatoid Arthritis (RA) For example, the cost for the new biological diseasemodifying anti-rheumatic drugs (DMARDs), such Rheumatoid arthritis (RA) is a common chronic as those that target tumour necrosis factor (TNF)-α, autoimmune disorder characterized by inflammation approaches $US16 000–20 000 (year 2007 pricing) annually per patient.[6] and damage of the articular cartilage, tendons and joints. The progressive nature of RA, especially if Use of DMARDs has transformed therapy of RA untreated or poorly treated, results in deformity of and is recommended early in the disease process the small joints of the hands and feet, the joints of (within 3 months of onset) to reduce disease activity wrists and shoulders, as well as rupture of damaged and achieve remission if possible.[7] A wide range of tendons in affected joints. In addition to causing biological and non-biological DMARDs are availdebilitating pain, swelling and stiffness of the affect- able, with the introduction of several new biological ed joints, RA may also cause extra-articular mani- agents in the last 5 years.[8] However, DMARDs festations (such as anaemia, interstitial inflamma- control rather than cure RA, and although complete tion of the lungs and glands, and nodules in the remission has been an infrequent occurrence with lungs, skin and eyes) that reduce survival. The pres- traditional DMARDs, a greater remission frequency ence of severe extra-articular manifestations, such may be possible with biological DMARDs.[8] as vasculitis, pericarditis, pleuritis or Felty’s syn- The chronic and lifelong nature of RA has shifted drome, has been associated with a particularly poor interest from purely symptomatic treatment to imprognosis that may result in premature mortality.[1] proving or restoring quality of life (QOL) as an RA is associated with significant morbidity and important therapeutic goal. The WHO defines QOL functional impairment. Study results have shown as “individuals’ perception of their position in life in that, within the first 18 months of RA onset, patients the context of their culture and value system in experience a substantial burden on physical func- which they live and in relation with their goals, tioning and emotional well-being that is comparable expectations, standards, and concerns.”[9] Healthto diabetes or heart failure.[2] In addition, RA results related QOL (HR-QOL) relates to the functional in a substantial economic burden to patients, their effects of an illness and of its therapy upon a patient, families, the healthcare system and society at large. and is often assessed using patient-completed quesFautrel and Guillemin[3] reported that the costs asso- tionnaires. In RA, HR-QOL includes several dimenciated with rheumatic diseases were even greater sions of health consequences, including pain, physithan those for either cancer or cardiovascular dis- cal functioning, stiffness, mental health, social funcease. tioning, fatigue and sleep disturbances.[10] The The economic burden of RA is only partially profound impact of RA on day-to-day life is reattributable to direct medical costs, which include flected in these HR-QOL dimensions. office visits, medications, surgeries and hospitaliza- Consequently, patient-reported outcomes, such tions. Indirect costs, which also contribute to the as HR-QOL, may be considered an important comeconomic burden, have been considered to be sub- ponent of therapeutic efficacy evaluations.[11] The stantially higher than direct costs.[4] These indirect increasing role of patient-reported outcomes is emcosts include lost productivity associated with work phasized by the recent US FDA draft guidance for disability and lost earnings.[4] It has been estimated industry on construction and use of appropriate inthat 50% of patients with RA are unable to function struments for measurement of these outcomes in at work within 10 years of disease onset.[5] How- clinical trials.[11] Additionally, HR-QOL may be ever, the difference between direct and indirect costs used in clinical practice to evaluate the overall im- © 2008 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2008; 26 (10)

QOL Assessment in Rheumatoid Arthritis 833 pact of ther y and to aid in treatment decisions for lobal health The several advantages of the DAS28 include its ability to evaluate disease ac. practice,physicians primarily evaluate the succe tivity and response to treatment independent of pre treatment status:its ability to discriminate betweer high and low disease activity:its sensitivity to treat Several validated instruments are available for clinical trials and clinical practice. statu fic dim en 3.QOL Assessment tings for aid in healthcare policy decisions.This article re. 3.1 Generic Instruments views several instruments that measure health status and HR-QOL in RA and provides examples of their There is no universal fo RA G of approac 2.Clinical Assessment of RA and table While ideally adi。 specific Disease Activity instrument should be used for many dise such instruments have not yet been developed for all There is no'gold standard'for measuring disease activity and remission in RA:however,physical, Although generic HR-QOL radiographic and laboratory measurements have tra ments are usually designed for the broadest possible se across a var ety or diseases,dilferent J01 an sme dcdneandd pain and icular appro Clinicians often rely on the American Colleg of population.These HR-QOL in Rheumatology (ACR)20.ACR50 or ACR70 res- struments are not only important in providing a ponse criteria to monitor a patient's response to means of comparison of effectiveness,but are also treatment.The ACR20 criteria have been validated key parameters that are incorporated into economic for use in clinical trials to define clinically signif analyses by capturing both benefi cial and detrimen provement(i.e tal effects tment on the individual.They are so use on across disease ve to the nu nd" An ted out the following nt as s is that of the mi an sessment,physician assessm difference (MCID).Clinical trial endpoints are gen of disability,and the value for one acute r erally evaluated for statistically significant differ. reactant (i.e.erythrocyte sedimentation rate [ESR] ences between treatment groups.However.what is or C-reactive protein [CRPD). statistically significant may not necessarily reflect a Another measurement of disease clinic Disease Activity S albenefit to the patient fa large enouh core (DAS)v is the which has d,even sm ences b er goticacaichtwiCe4gnicatwiho dinde that is based on of the MCID vid that dis n statistical and and tender joints (of 28 joints).the ESR,and a visual clinical relevance The MCI refers to the small- analogue scale score (0-100)of patients'general or est difference in an outcome that is perceived by the 2008 Adis Data Information BV.All rights reservod. Pha conomics2008:26(10)

QOL Assessment in Rheumatoid Arthritis 833 pact of therapy and to aid in treatment decisions for global health.[14] The several advantages of the the individual patient. However, in current clinical DAS28 include its ability to evaluate disease acpractice, physicians primarily evaluate the success tivity and response to treatment independent of preof therapy from a clinical perspective and rarely treatment status; its ability to discriminate between assess HR-QOL.[10,11] high and low disease activity; its sensitivity to treatSeveral validated instruments are available for ment effects; as well as its validation for use both in clinical trials and clinical practice.[13] evaluation of HR-QOL, and while some of these instruments characterize the health status of an individual or population with regard to specific dimen- 3. QOL Assessment sions or domains, others can be used to derive utility weightings for use in economic evaluations, and to 3.1 Generic Instruments aid in healthcare policy decisions. This article reviews several instruments that measure health status There is no universally accepted definition of, or and HR-QOL in RA and provides examples of their method for measuring, disease-specific HR-QOL in use in clinical trials of the newest biological RA. General features of approaches utilized to mea- DMARDs for the treatment of RA. sure HR-QOL in RA are represented in figure 1[15,16] and table I.[15,17-20] While ideally a disease-specific 2. Clinical Assessment of RA instrument should be used for many diseases, such Disease Activity instruments have not yet been developed for all There is no ‘gold standard’ for measuring disease disease states, and generic instruments are often utilized.[15,20] activity and remission in RA; however, physical, Although generic HR-QOL instruradiographic and laboratory measurements have tra- ments are usually designed for the broadest possible ditionally been used, often in combination. use across a variety of diseases, different medical [8] These interventions and a wide range of populations, measures include counting of inflamed joints, as- [21] sessment of degree and duration of pain and stiff- specific or targeted instruments may be more approness, and clinician and patient global assessments. priate than generic measures for a particular setting, [8] or in a defined population.[21] Clinicians often rely on the American College of These HR-QOL inRheumatology (ACR) 20, ACR50 or ACR70 res- struments are not only important in providing a ponse criteria to monitor a patient’s response to means of comparison of effectiveness, but are also treatment. The ACR20 criteria have been validated key parameters that are incorporated into economic for use in clinical trials to define clinically signif- analyses by capturing both beneficial and detrimenicant levels of improvement. tal effects of treatment on the individual. They are [12] Patients are required to have a minimum level of improvement (i.e. 20%, also useful for outcomes comparison across disease 50% or 70%) relative to baseline in the number of states and can aid in policy decisions. swollen joints and tender joints, and in any three of An important concept in patient-reported outthe following disease-activity measures: patient as- comes is that of the minimal clinically important sessment, physician assessment, pain scale, degree difference (MCID). Clinical trial endpoints are genof disability, and the value for one acute phase erally evaluated for statistically significant differreactant (i.e. erythrocyte sedimentation rate [ESR] ences between treatment groups. However, what is or C-reactive protein [CRP]).[8] statistically significant may not necessarily reflect a Another measurement of disease activity is the clinical benefit to the patient (i.e. if a large enough Disease Activity Score 28 (DAS28), population is used, even small differences between [13] which has been more frequently used in Europe, but is gaining treatments may be statistically significant without being of actual clinical value).[25] wider acceptance in the US in clinical trials as well as in clinical practice. This scoring system is a The concept of the MCID was initiated to provide combined index that is based on a count of swollen a measure that distinguishes between statistical and and tender joints (of 28 joints), the ESR, and a visual clinical relevance.[26] The MCID refers to the smallanalogue scale score (0–100) of patients’ general or est difference in an outcome that is perceived by the © 2008 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2008; 26 (10)