834 Russell Health-related quality of life Taxonomy Health status Value or preference Global value assigned to the health state dHealth state system sF-36 HAG-DI nts to measure health-related quality of life Reproduced from Khanna et a)with pemmission from earch.HAQ-DI Health Asses patient to be of clinical benefit:th MCID is s unrela- Correlation of HAQ-DI scores with improve ted to statis I significance. Although MCID is ments physic 0Q0 measures,It may also be of HAQ-D r oth rele vant or paned t-re eive as he neficial.In the RA setti improvement of at least 0.22 is considered indica s an efficacy ou s in a tive of improved functional status,while smaller improvements are considered unimportant30 The Personal-Impact HAQ(PI-HAQ).developed in the The Health Assessment Ouestionnaire (HAO) the HAQ was among the first instruments created that focused instrument on patient self-reported measures of functional sta- tus and disability although the hao is not disease by the Lomspecifcd specific.it was developed for use in patients with enhance the xtual inter RA and was validated in this population.The retation of the Had it has vet to be accer nted as a thd mee ou e standard measurement instrument.Although the HAQ does not directly measure psychological do version most often used in RA assessment is the mains,responses on the HAQ appear to reflect pa- HAQ Disability Index(HAQ-DD).which consists of tient psychological status. 20 questions that assess eight domains of disability. The SF-36 is a well validated s eric instrumen dressing,arising,eating,reaching,gripping,walk for evaluating health status.and is frequently used in the assessment of HR-QOL in RA.This instrument includes eight scales,each of which evaluates a particular domain (physical functioning.role limita severe/very severe due to phys oning,role
834 Russell Indirect Health-related quality of life: Taxonomy Health status Value or preference Describes health states and impact on function and disability Global value assigned to the health state Health state classification system Direct Rating scale Time trade-off Standard gamble Objective • joint count • exercise tests • visual acuity Subjective • reports, ratings • functional capacity • symptoms • feelings • behaviour Generic SF-36 Disease-specific HAQ-DI Fig. 1. Taxonomy of instruments to measure health-related quality of life.[15,16] Reproduced from Khanna et al.[15] with permission from Scleroderma Care and Research. HAQ-DI = Health Assessment Disability Index. patient to be of clinical benefit; the MCID is unrela- Correlation of HAQ-DI scores with improveted to statistical significance. Although MCID is ments in various physical parameters in RA has often applied to QOL measures, it may also be allowed determination of the MCID in HAQ-DI derived for other clinically relevant or patient-re- scores, defined as the smallest difference that paported outcomes.[27] MCID is currently considered tients perceive as beneficial. In the RA setting, an improvement of at least 0.22 is considered indica- as an efficacy outcome for trials in a variety of tive of improved functional status, while smaller disease states, and its derivation, usefulness and improvements are considered unimportant.[30,31] The limitations have been discussed.[25,27] Personal-Impact HAQ (PI-HAQ), developed in the The Health Assessment Questionnaire (HAQ)[28] UK, adapts the HAQ for assessing the personal was among the first instruments created that focused impact of disability. This instrument accounts for on patient self-reported measures of functional sta- the value placed by the patient on specific disabilitus and disability. Although the HAQ is not disease ties by using an individualized impact scale.[32] specific, it was developed for use in patients with While this scale may enhance the contextual interRA and was validated in this population.[29] The pretation of the HAQ, it has yet to be accepted as a HAQ has subsequently become the most widely standard measurement instrument. Although the used measure of functional disability in RA.[18] The HAQ does not directly measure psychological doversion most often used in RA assessment is the mains, responses on the HAQ appear to reflect patient psychological status.[33] HAQ Disability Index (HAQ-DI), which consists of 20 questions that assess eight domains of disability: The SF-36 is a well validated generic instrument dressing, arising, eating, reaching, gripping, walk- for evaluating health status, and is frequently used in ing, activities and hygiene. The total score of the the assessment of HR-QOL in RA. This instrument HAQ-DI ranges from 0 to 3, with scores of 0–1 includes eight scales, each of which evaluates a indicating mild/moderate disability, 1–2 moderate/ particular domain (physical functioning, role limitasevere disability and 2–3 severe/very severe disabil- tions due to physical health, bodily pain, general ity.[29] health perceptions, vitality, social functioning, role © 2008 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2008; 26 (10)
QOL Assessment in Rheumatoid Arthritis 835 limitations due to emotional health,and mental (tility score)that describes a particular health health).as well as two summary score each for he physical and mental state Utilities are derived from health status by provement in any of the domains of three points is considered to be a change that represents the MCID. The SF-36 is one of the most commonly used HR- ealth st perfect he worse than death can Q0 50 diferent languages. Two common health utilities are the standard 3.2 Health Utilities gamble and the time trade-off,which assess what trade-offs (such as increased risk of death or how many months of life)the patient would make for a better health state.37 Scores on these tests may uating different domains,generic health utilities are range from 0.0 to 1.0.Another type of approach is measures that summarize HR-QOL as a single value the rating scale and as described above,patients rate stics of c used hea -related au of-ite (HR-OOL)instruments in rheumatoid arthritis (RA to Adva Generic measures HAQ-DI 20 5 Can be diseases and May not be as sensitive to ss di may o SF-36 36 5 Ca aom ms,heah and y3e-p9cfC age ranges;self-administered 67 15 30 diae ,6 Ith utility me HUI2 405 or Provides a single HR-QOL number re,p HUI3 15 or As above As above nion,pain edery.emoton SF-6D 11 As above As above E0-5D° As above As above a Five items plus HAQ-DI=Health Assessment Questionnaire Disability Index HUI=Health Utilities Index 2008 Adis Data Information BV.All rights resorved Phamocooconomics 2008:26 (10)
QOL Assessment in Rheumatoid Arthritis 835 limitations due to emotional health, and mental (utility score) that describes a particular health health), as well as two summary scores, one each for state.[37] Utilities are derived from health status by the physical and mental components.[34,35] An im- assigning population-based weights based on preferprovement in any of the domains of three points is ences for health states, and are usually expressed on considered to be a change that represents the MCID. a continuum from perfect health (1) to death (0), The SF-36 is one of the most commonly used HR- although health states worse than death can also be QOL instruments and has been translated into over valued.[37] 50 different languages.[36] Two common health utilities are the standard gamble and the time trade-off, which assess what 3.2 Health Utilities trade-offs (such as increased risk of death or how In contrast with the above generic instruments, many months of life) the patient would make for a better health state.[37] which describe an individual’s health status by eval- Scores on these tests may uating different domains, generic health utilities are range from 0.0 to 1.0. Another type of approach is measures that summarize HR-QOL as a single value the rating scale and as described above, patients rate Table I. Characteristics of commonly used health-related quality-of-life (HR-QOL) instruments in rheumatoid arthritis (RA)[15,17-20,22-24] Measure Items (n) Aspects assessed Minutes to Advantages Disadvantages complete Generic measures HAQ-DI 20 Activities of daily living: dressing, 5 Can be used across diseases and May not be as sensitive to arising, eating, walking, hygiene, populations; allows comparison change as disease-specific reach, grip, activities across diseases, levels of health and measures; may not age ranges; self-administered provide a single summary score SF-36 36 Physical function, role limitations 5 Can be used across diseases and May not be as sensitive to due to physical problems, health populations; allows comparison change as disease-specific perception, vitality, pain, social across diseases, levels of health, and measures; may not function, mental health role age ranges; self-administered provide a single summary limitations due to emotional score problems RA-specific measures AIMS 67 Physical activity, activities of daily 15 Self-administered; high reliability, Only applicable to certain living, dexterity, mobility, social validity, and sensitivity; more sensitive diseases or conditions role and activity, pain, depression, to change than generic measures; anxiety validity for specific population RAQoL 30 Mood/emotion, social life, hobbies, 6 Self-administered; high reliability, Only applicable to certain everyday tasks, personal/social validity, and sensitivity; more sensitive diseases or conditions relationships, physical contact to change than generic measures; validity for specific population Health utility measures HUI2 15 or Sensation (vision, hearing, Provides a single HR-QOL number May not be as sensitive to 40 speech), mobility, emotion, change as health status cognition, self-care, pain measures HUI3 15 or Vision, hearing, speech, As above As above 40 ambulation, dexterity, emotion, cognition, pain SF-6D 11 Physical function, role limitation, As above As above social function, pain, mental health, vitality EQ-5D 6a Mobility, usual activities, self-care, As above As above pain, anxiety a Five items plus a visual analogue scale. AIMS = Arthritis Impact Measurement Scales; HAQ-DI = Health Assessment Questionnaire Disability Index; HUI = Health Utilities Index; RAQoL = Rheumatoid Arthritis Quality of Life. © 2008 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2008; 26 (10)
836 Russell their health on a continuum from perfect health (1) quantity and quality of life into a single measure to death(0).although health states worse than death For economic analyses,the cost per QALY can be can also be valued and aregenerally represented by negative Index (HUI and sused to calculate OALYs should be n he fully correlated with patient behaviour before these instruments are not interehane eable.caution must be values are used in healthcare decision making.44 3.3 Disease-Specific Instruments The EO-5D.a generic health index developed in the 1990s,derives and evaluates utilities associated Among the most widely used disease-specific with HR-QOL.Although the original form included instruments in RA are the Arthritis Impact Measure. six attributes,the current version is composed of two e e m R and the Rheumatoid Arthritis Quality of nd co e do usual activities.pain/discomfort and anxiety/dep ial inte and affect).A sion.Scores on the EQ-5D range from 1 (perfect ture of the AIMS2 is a section on prior which patients can select three of 12 areas in which health)to-o 59 (worse than dead).A short adminis- tration time and the availability of pre-scored nor- they would like to see improvements during treat- mative values in several populations make the ment (e.g.pain,mobility,work).RAQoL,a 30-item EQ-5D easy to h a yes/no response format,assesse RA.Homajor mood.so ial life,hobbi veryday tasks.person d ha RAOo d the Neth other me ed fo validated in RA.4 Two HUI question cluding sweden ia.Turkey Australia.Its advantages include a direct rele speech ambulation.dexterity vance to items and issues of importance to patients. emotion.cognition and pain)that are scaled on as well as ease of use and short administration time. making it accessible for use in clinical practice. several levels from normal to highly impaired,4 and the HUI2,while similar to the HUI3,is also &eoaeeeatnnmentn ng sens In general,heumatologists have not yet incorpo rated rout of pat health)to (dead) s HR-QOL The SE-6D.another health utility instrum ent.is such 、E based on the SE-36 and SE-12 22 Six domains from rheumatologists who do utilize these instruments in the SF-36 (physical functioning,role limitations everyday practice,the effect on decision making is social functioning.pain.mental health and vitality) not clear are used to calculate a utility score based on weight To address this issue in part,the sixth biannual conference of the Outcome Measures in Rheuma toid Arthritis Clinical Trials group(OMERACT) lues are use developed to combine h
836 Russell their health on a continuum from perfect health (1) quantity and quality of life into a single measure.[43] to death (0), although health states worse than death For economic analyses, the cost per QALY can be can also be valued and are generally represented by estimated and compared among the evaluated theranegative values (i.e. <0).[37] pies. However, it has been suggested that the underThe EQ-5D, Health Utilities Index (HUI) and lying assumptions associated with health utility SF-6D are multi-attribute generic instruments that measures used to calculate QALYs should be carecan be used to calculate utility values. fully correlated with patient behaviour before these [37] Since these values are used in healthcare decision making.[44] instruments are not interchangeable, caution must be taken when comparing studies that have used these different instruments. 3.3 Disease-Specific Instruments [37] The EQ-5D, a generic health index developed in Among the most widely used disease-specific the 1990s, derives and evaluates utilities associated instruments in RA are the Arthritis Impact Measure- with HR-QOL. Although the original form included ment Scales (AIMS)-2, a revised version of the six attributes, the current version is composed of two AIMS,[45] and the Rheumatoid Arthritis Quality of parts, a questionnaire and visual analogue self-rating Life (RAQoL) questionnaire.[23] The multi-dimen- scale.[38,39] The questionnaire includes components sional AIMS2 contains items in 12 areas of health of functionality, pain and psychiatric well-being, that can be grouped in five major domains (physical, and focuses on the five domains: mobility, self-care, social interaction, pain, work and affect). A unique usual activities, pain/discomfort and anxiety/depres- feature of the AIMS2 is a section on priorities, in sion. Scores on the EQ-5D range from 1 (perfect which patients can select three of 12 areas in which health) to –0.59 (worse than dead). A short adminis- they would like to see improvements during treat- tration time and the availability of pre-scored nor- ment (e.g. pain, mobility, work). RAQoL, a 30-item mative values in several populations make the instrument with a yes/no response format, assesses EQ-5D easy to use. The EQ-5D is now widely used mood, social life, hobbies, everyday tasks, personal/ internationally, has been translated into most major social relationships and physical contact.[23] The languages[38] and has been validated in RA.[40] RAQoL was developed in the UK and the Nether- Another health utility measure, the HUI, is a lands,[23] and has been adapted for use in several multi-attribute classification system that has been countries, including Sweden, Estonia, Turkey and validated in RA.[40] Two HUI questionnaires are Australia.[46-48] Its advantages include a direct rele- currently used: the HUI3 consists of eight attributes vance to items and issues of importance to patients, (vision, hearing, speech, ambulation, dexterity, as well as ease of use and short administration time, emotion, cognition and pain) that are scaled on making it accessible for use in clinical practice. several levels from normal to highly impaired,[41] and the HUI2, while similar to the HUI3, is also 4. Use of Assessment Instruments in complementary by providing assessment of inde- Clinical Practice pendent attributes, including sensation, mobility, emotion, cognition, pain, fertility and self-care.[42] In general, rheumatologists have not yet incorpoUtility scores on the HUI range from 1 (perfect rated routine assessment of patient-reported outhealth) to 0 (dead). comes such as HR-QOL into everyday clinical pracThe SF-6D, another health utility instrument, is tice, mainly because of time considerations.[49] For based on the SF-36 and SF-12.[22] Six domains from rheumatologists who do utilize these instruments in the SF-36 (physical functioning, role limitations, everyday practice, the effect on decision making is social functioning, pain, mental health and vitality) not clear. are used to calculate a utility score based on weight- To address this issue in part, the sixth biannual ed preferences for health states derived from exten- conference of the Outcome Measures in Rheumasive interviews in the general population.[22] toid Arthritis Clinical Trials group (OMERACT)[50] Instruments that determine utility values are use- has encouraged novel ways to incorporate patient ful for calculating QALYs, developed to combine perceptions into outcomes research. Patients partici- © 2008 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2008; 26 (10)
QOL Assessment in Rheumatoid Arthritis 837 ating in this confer the HAQ that were clinically relevant and statistical- ly significant compared with patients who received mspacR methotrexate monotherapy.QOL benefits were also uggested by significant improvements from base. well-being.Is Instruments with on-the-spot scoring line in the physical component summary score and te)shoul a broaden the applicability of pa puter sys outcomes in clinical practice indivdWhile general health.vitality and social unction s were also significantly 5.Do Current Treatments Improve QOL in RA? ent summary score.In contrast.when Han et eutic a nts such as the biolo cal DMARDs.sev studies were in RA)given infliximab at similar eral of which are available for use in the yreatment doses plus methotrexate at various time points for up were found. of RA.Biological DMARDs currently approved to 1 year,different rsu At the firs we in on for the treatment of RA include infliximab time point of e adalimumab.etanercept,anakinra,rituximab and or ents in the aysical com ase progres re.in addition to small though statistically signif onent sum add ntial to in rove HR-QOL has results in Maini et al,paralleled improvements in clinical outcomes with significantly less radiograph- 5.1 Infliximab ic progression and a significantly than ong patien Infliximab is a chimeric(murine/human)mono erapy clonal antibody against TNFo,a cytokine secreted as a reaction to injury during the inflammatory res- 5.2 Adalimumab inflammation and incr ses Adalimumab,like infliximab,is an anti-TNFo ing immune cells to g the TNFo of infl ons of ce ab is cells t57 Adalim ated ing signs and symptoms.inhibiting the for reducing signs and symptoms.inducing major clinical response,inhibiting the progression of struc. tural damage and improving physical function in dult patients with moderately to severely active Functional and QOL outcomes associated with use of infliximab (3 mg/kg or 10 mg/kg every 4 or me mbinatio hile a in a 2 otherapy.as -ye with tha ed th ks of the dalimumab ther apy alone.more Using data from two trials of adalimumab plus from baseline in physical function as measured by methotrexate versus methotrexate alone in patients conomics2008:26(100
QOL Assessment in Rheumatoid Arthritis 837 pating in this conference agreed that standard core the HAQ that were clinically relevant and statisticalRA criteria do not adequately capture some conse- ly significant compared with patients who received quences of the disease that are of importance to methotrexate monotherapy. QOL benefits were also them, including fatigue, disturbed sleep and sense of suggested by significant improvements from basewell-being.[51] Instruments with on-the-spot scoring line in the physical component summary score and and technology (such as touch-screen computer sys- individual physical domain components of the tems) should also broaden the applicability of pa- SF-36.[59] While general health, vitality and social tient-reported outcomes in clinical practice.[52] functioning subscale scores were also significantly improved compared with baseline and methotrexate, 5. Do Current Treatments Improve QOL no significant changes were noted on the mental in RA? component summary score. In contrast, when Han et al.[60] analysed results from four studies in patients A better understanding of the pathophysiology of with inflammatory rheumatic disease (of which two RA has resulted in the development of new thera- studies were in RA) given infliximab at similar peutic agents such as the biological DMARDs, sev- doses plus methotrexate at various time points for up eral of which are available for use in the treatment to 1 year, different results were found. At the first of RA. Biological DMARDs currently approved assessment time point of either 6 weeks in one study for the treatment of RA include infliximab, or 10 weeks in the second study, data from these adalimumab, etanercept, anakinra, rituximab and studies showed patients with RA had significant abatacept.[53-58] These agents not only control symp- improvements in the physical component summary toms and slow radiographic disease progression, but score, in addition to small though statistically signif- hold forth the possibility of achieving disease remis- icant improvements in the mental component sum- sion. In addition to their established clinical effi- mary score compared with baseline.[60] The QOL cacy, their potential to improve HR-QOL has been results in Maini et al.[59] paralleled improvements in evaluated in several studies. clinical outcomes with significantly less radiographic progression and a significantly better ACR res- 5.1 Infliximab ponse rate among patients in the infliximab groups than with methotrexate monotherapy. Infliximab is a chimeric (murine/human) monoclonal antibody against TNFα, a cytokine secreted 5.2 Adalimumab as a reaction to injury during the inflammatory response. TNFα promotes inflammation and increases Adalimumab, like infliximab, is an anti-TNFα blood vessel permeability, enabling immune cells to agent. Although adalimumab is a fully human antiinfiltrate the joints.[58] By blocking the actions of body, in contrast to the chimeric properties of inflixTNFα, infliximab reduces the number of inflamma- imab, the mechanism of action is the same: binding tory cells migrating into the joints. When combined of TNFα, whether soluble or on the surface of with methotrexate, infliximab is indicated for reduc- TNFα-expressing cells.[57] Adalimumab is indicated ing signs and symptoms, inhibiting the progression for reducing signs and symptoms, inducing major of structural damage, and improving physical func- clinical response, inhibiting the progression of struction in patients with moderately to severely active tural damage and improving physical function in RA.[58] adult patients with moderately to severely active Functional and QOL outcomes associated with RA, and may be used as monotherapy or in combination with methotrexate or other DMARDs.[57] use of infliximab (3 mg/kg or 10 mg/kg every 4 or 8 weeks) in combination with methotrexate were While adalimumab is approved for monotherapy, as evaluated in a 2-year study (placebo controlled for observed with other anti-TNFα therapies, combina- 1 year then open label) by Maini et al. tion with methotrexate is more effective than [59] They adalimumab therapy alone.[57] reported that, after 102 weeks of therapy, patients who received infliximab showed improvements Using data from two trials of adalimumab plus from baseline in physical function as measured by methotrexate versus methotrexate alone in patients © 2008 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2008; 26 (10)
838 Russell with RA.Torrance et al.reported changes in activity (numeric rating scale).patient general o e orms.as a meas treatmen ecei ed Hr-OOl n therapy hac QOL POP ciated with significantly s with lower scores in those HUI attributes that may be ed the HA-DI.com ared with those expected to be reduced as a result of RA:pain, who received either monotherapy.Improvements in dexterity and ambulation.However,other attributes HR-QOL were more rapid and were sustained long er in the combination therapy group than in eithe lation norms monotherapy group (combination vs methotrexate in total HUI3 Crreres.ved with adalimum p=0.005:combi 30.00 exter the duration of the trials.which ained ma e,p as lon nd than with 1 vear.These im ments wer significantly - thotrexate perior to those observed with methotrexate mono In contrast,Farahani et al.conducted a 1-year therapy.While improvements in ambulation were community-based study that compared patients with also noted,this only reachec statistical significance RA who were able to obtain etanercept after its relative to methotrexate in the 1-year study.Higher on into the Canadian market (active treat ment,n=223)with those unable to obtain this agen pumher of OALYs lone.Th ined tients a other the 12-m ate was 0.145 and 0.104 in the two studies.and was cause of improved physical (rather than emotional statistically significant (p<0.001). or mental)parameters,improvements in QOL were documented within the first 6 months in patients who received etanercept compared with those who While is als nti-TN did not.However,this difference between groups ne onsignificant r some QOL e of .es tigue inten y,dur y he and adalimumab.Etanercept is a recombinant obtained in the TEMPO(Trial of Etane cept and Methotrexate with radioo nhic patient outeomes trial of etanercept and methotrexate2 highlight the for red inducing major clinic differences that may often be observed betweer 10 also carry over into economic analyses. Patient-reported outcome 5.4 Anakinro were evaluated in a I-vear randomized double-blind clinical trial of Anakinra is a recombinant interleukin(IL)-1 re- etanercept in combination with methotrexate com- eptor antagonist that is similar to the endogenous pared with either DMARD as monotherapy.Out- IL-1 receptor antagonist (IL-Ira).Like TNFo,IL- s a pro-infla heDe truments such as and th Q-5D visual ana receptor,anaki mmatory response Ahodowaegu ough anakinra h
838 Russell with RA, Torrance et al.[61] reported changes in activity (numeric rating scale), patient general health utility using the HUI3, compared with popu- health assessment (visual analogue scale) and palation norms, as a measure of HR-QOL.[61] Baseline tient satisfaction with treatment.[62] Patients who HUI3 scores were significantly lower (p < 0.001) received combination therapy had significantly imthan population norms,[61] and this reduction in HR- proved HR-QOL and were more likely to achieve QOL was primarily associated with significantly population norms with regard to function, as indicatlower scores in those HUI attributes that may be ed by scores on the HAQ-DI, compared with those expected to be reduced as a result of RA: pain, who received either monotherapy. Improvements in dexterity and ambulation. However, other attributes HR-QOL were more rapid and were sustained longalso showed significant reductions relative to popu- er in the combination therapy group than in either lation norms.[61] Rapid improvements from baseline monotherapy group (combination vs methotrexate, in total HUI3 scores, as well as in the attributes of p = 0.005; combination vs etanercept, p = 0.002; pain and dexterity, were observed with adalimumab etanercept vs methotrexate, p = 0.780).[62] Patients plus methotrexate treatment and were sustained over also reported significantly greater satisfaction with the duration of the trials, which was as long as combination and etanercept monotherapy than with 1 year. These improvements were significantly su- methotrexate monotherapy.[62] perior to those observed with methotrexate mono- In contrast, Farahani et al.[63] conducted a 1-year therapy.[61] While improvements in ambulation were community-based study that compared patients with also noted, this only reached statistical significance RA who were able to obtain etanercept after its relative to methotrexate in the 1-year study. Higher introduction into the Canadian market (active treatproportions of adalimumab-treated patients ment, n = 223) with those unable to obtain this agent achieved or exceeded HUI3 population norms than (control, n = 208). As a reflection of actual clinical patients treated with methotrexate alone.[61] The practice, these patients had no previous treatment number of QALYs gained per year among with etanercept, and no restrictions were placed on adalimumab-treated patients relative to methotrex- other therapies during the 12-month study.[63] Beate was 0.145 and 0.104 in the two studies, and was cause of improved physical (rather than emotional statistically significant (p < 0.001). or mental) parameters, improvements in QOL were documented within the first 6 months in patients 5.3 Etanercept who received etanercept compared with those who While etanercept is also an anti-TNF did not. However, this difference between groups α agent that decreased or became nonsignificant for some QOL binds to TNF and blocks its interaction with cell variables, especially pain severity and fatigue inten- receptors on the cell surface, it is a different type of sity, during the second 6 months.[63] The apparent entity from the monoclonal antibodies infliximab inconsistency between these QOL results and those and adalimumab. Etanercept is a recombinant obtained in the TEMPO (Trial of Etanercept and human fusion protein for the soluble TNFα recep- Methotrexate with radiographic Patient Outcomes) tor.[56] It may be used as monotherapy or in combi- trial of etanercept and methotrexate[62] highlight the nation with methotrexate, and is indicated for reduc- differences that may often be observed between ing signs and symptoms, inducing major clinical clinical trials and clinical practice, and which may response, inhibiting the progression of structural also carry over into economic analyses.[63] damage and improving physical function in patients with moderately to severely active RA.[56] 5.4 Anakinra Patient-reported outcomes were evaluated in a 1-year randomized double-blind clinical trial of Anakinra is a recombinant interleukin (IL)-1 reetanercept in combination with methotrexate com- ceptor antagonist that is similar to the endogenous pared with either DMARD as monotherapy. Out- IL-1 receptor antagonist (IL-1ra). Like TNFα, IL-1 comes included standard QOL instruments such as is a pro-inflammatory cytokine, and by blocking its the HAQ-DI and the EQ-5D visual analogue scale, access to the IL-1 receptor, anakinra may downreguas well as patient global assessment of RA disease late the inflammatory response. Although anakinra © 2008 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2008; 26 (10)