Rheumatoid arthritis: recommendations for treat to target Deborah Palmer and Yasser El Miedany
Abstract
Integrating the rheumatoid arthritis (RA) treat-to-target concept into standard clinical practice represents a challenge to health professionals. So far, this practice-changing approach has not been widely implemented, in spite of linking its outcome to payment, which was adopted in the best practice tariffs. The recently published revisions in classification criteria and updated recommendations for optimising the use of disease-modifying anti-rheumatic and biologic agents in the treatment of RA paved the way for re-evaluating the standard clinical care models in order to improve patient outcomes, prevent joint damage, and maintain patients’ functional ability as well as their quality of life. This article discusses the recent advances in the management of RA and provides a set of recommendations to provide comprehensive guidance for treatment to target with the aim of improving the quality of care for RA patients. Key words: Treat to target ■ Rheumatoid arthritis ■ Patient-reported outcome measures (PROMs) ■ Patient-reported experience measures (PREMs) ■ Ultrasound
O
ver the past few decades, a revolution has occurred in the management of rheumatoid arthritis (RA), which has completely changed the way RA patients are managed in standard clinical practice. It started with identifying outcome measures and, later, the development of scores to assess RA disease activity reliably. The development of objective tools, such as the American College of Rheumatology (ACR) response criteria (Felson et al, 1993) and the Disease Activity Score (DAS) (van der Heijde et al, 1993), formed the cornerstone for all clinical trials carried out to assess arthritis treatment. The development of a scoring system for the assessment of radiological impact of the disease on the joints, which highlights the importance of disease control (Sharp et al, 1971), was followed by the development of the functional disability score tool Health Assessment Questionnaire (HAQ) in the early 1980s (Fries et al, 1980), which helped to personalise the treatment of the disease and assess its impact on patients’
lives. These tools enabled the evaluation of the standard drug treatments known as disease-modifying anti-rheumatic drugs (DMARDs), which include methotrexate, leflunomide and sulphasalazine, azathioprine, hydroxychloroquine, and gold injections. Subsequently, the outlook for RA treatment has changed and formed a quantum leap over the previously adopted treatment pyramid (Bensen et al, 1997). The introduction of biologic therapy in the late 1990s also enabled the attainment of unprecedented outcomes for patient care (Feldmann and Maini, 2003; Smolen et al, 2003; Aletaha et al, 2005). These three phases led to the biggest change in RA treatment goals and the introduction of the definition of remission, which means real disease control with no pain, stiffness, swelling or joint damage. Hence, the treatment paradigm changed to adopt the ‘treat-to-target’ approach aiming at disease remission (Smolen et al, 2010). The concept of achieving tight control of RA and treating to target entails: ■■ Early diagnosis ■■ Early and progressive treatment ■■ Regular monitoring. This is expected to lead to positive outcomes in a significant number of RA patients who achieve treatment goals of either clinical remission or low levels of disease activity. As adopting such an approach in standard clinical practice has been linked to payments in what is called ‘best practice tariff ’ (Department of Health (DH), 2013), and in view of the traditional pressure in rheumatology outpatient services, rheumatology specialist nurses and middle-grade health professionals are expected to play an important role in executing this treatment approach. This article provides a set of recommendations to provide comprehensive guidance for treatment to target (Figure 1) and help improve the quality of care for RA patients in clinical practice as set out in the Commissioning for Quality in Rheumatoid Arthritis (CQRA) guidelines (National Rheumatoid Arthritis Society, 2012). The consensus finding was evidence-based, obtained from a systematic literature review and the recently published European League Against Rheumatism (EULAR) guidelines, which revealed improved outcomes with strategic therapeutic approaches (Schoels et al, 2010; Smolen et al, 2013).
Accepted for publication: February 2014
This concept of targeted treatment is closely related to the notion of tight control, which is the practice of measuring disease activity at regular intervals of weeks or months, making sure that the target is met, or adjusting the treatment so that it will be met the next time (van den Broek et al,
310
British Journal of Nursing, 2014, Vol 23, No 6
British Journal of Nursing 2014.23:310-315.
© 2014 MA Healthcare Ltd
Treat to target Deborah Palmer is Advanced Nurse Practitioner, North Middlesex University Hospital, London; Yasser El Miedany is Consultant Rheumatologist, Darent Valley Hospital, Dartford
RHEUMATOID ARTHRITIS 2012). In inflammatory arthritis, the target is to achieve disease remission or a low disease activity state.
Challenges and proposed solutions However, in day-to-day practice, trying to adopt this approach, which should be tailored to the patient’s condition, usually comes with challenges, among which the time factor comes first. In the early inflammatory arthritis (EIA) model defined by ‘best practice tariff ’ recommendations, patients referred with suspected EIA should have their first specialist appointment within 3 weeks of their referral date (DH, 2013). Within 6 weeks of referral, diagnostic testing and any necessary clinical reviews should be completed so that by the end of this 6-week period, people who do not have EIA should be discharged back to the care of their GP, and those with EIA should have received their first prescription for disease-modifying therapy. To meet this challenge, a dedicated outpatient service aimed at seeing this group of patients within 3 weeks would need to be set up. In centres where the workload hinders such timed early patient assessment, setting up a dedicated clinic or nurse-led early arthritis service has proved to be workable and successful (El Miedany et al, 2006). Agreeing a referral pathway with the primary care physician for baseline lab investigation prior to the referral would also help in shortening diagnosis time (El Miedany et al, 2005). The second challenge is the pressure of close monitoring of patients diagnosed as having EIA (Figure 2) to assess for their disease activity and response to therapy, especially in the first year of therapy, which obliges senior health decisionmakers to handle the issue with no further increase in the budget. This is best handled through a service working as a multidisciplinary team, where the patients are to be reviewed by the rheumatology nurses, adopting an agreed treatment protocol (El Miedany et al, 2006). Last, the frequency with which RA patients are evaluated for their achievement of target represents a third challenge. Rheumatology nurses play an important role in facing this challenge. However, in most cases, this might be variable as the frequency of evaluation and monitoring of disease activity should ultimately depend on the patient’s level of disease activity; patients with higher disease activity would require more frequent monitoring (El Miedany et al, 2005).
© 2014 MA Healthcare Ltd
Treatment protocol and decision As the RA treatment paradigm has changed to a patientcentred model since the publication of guidelines from the National Institute of Health and Care Excellence (NICE) in 2009, treatment of the disease should be based on a shared decision between patient and rheumatologist with abrogation of inflammation being the most important goal to achieve desired treatment targets. In concordance with NICE guidelines, the EULAR has released updated recommendations (Smolen et al, 2013) for the management of RA. According to this latest guidance, treatment with DMARDs should be initiated as soon as a diagnosis of RA is made, with the aim of reaching a target of remission (DAS282.6–2.6-3.2 - 5.1
Features of Poor Prognosis*
DMARD Combination therapy
DMARD Monotherapy (Methotrexate 20-25mg/wk)
Assess Disease Activity after 3m Moderate or High Activity
Low Disease Activity Up DMARD Monotherapy dose/ Or Combination Therapy
Add or switch DMARD Try new double/ Triple combination
Moderate Disease Activity
Continue if in remission
Continue if in remission
+ Combined with IM/ short term Low/high steroids
Assess Disease Activity after 3m
High Disease Activity: DAS-28 > 5.1 MTX + Anti-TNF: Adalimumab/ Certolizumab / Etanercept / Golimumab / Infliximab or Tocilizumab or Abatacept
High Disease Activity: DAS-28 > 5.1 The patient is intolerant to MTX, or MTX treatment is considered to be inappropriate Anti- TNF: Adalimumab/ertolizumab/ Etanercept or Tocilizumab
Assess After 3m & 6 m
The Biologic has been withdrawn because of an adverse event within first 6 months of treatment
Consider alternative Biologic Therapy
Adequate response to treatment at 6-months (DAS28 score improved by ≥ 1.2): Continue Treatment
Maintain same treatment / adjust DMARDs dose to achieve remission &monitor patient every 6m
No Adequate response to treatment at 6-months (DAS28 score improved by< 1.2)
Consider alternative Biologic inhibitor (Including Rituximab + MTX)
et al, 2005) Therefore, a more appropriate target disease state should be sustained remission (the absence of disease activity and flare over the longest possible period of time). This may be more difficult to achieve as data suggest that approximately half of RA patients in remission may experience a disease flare within 24 months. Flare has been shown to be associated with more radiographic progression when compared with patients in sustained remission (Molenaar et al, 2004) Therefore, in
standard clinical practice, once remission is achieved, the treating health professional needs to be confident that the patient will maintain this state in order to ensure the best possible outcomes.
One-stop service Taking into consideration the rate at which different patients achieve their targets, the speed with which they achieve their
312
British Journal of Nursing, 2014, Vol 23, No 6
British Journal of Nursing 2014.23:310-315.
© 2014 MA Healthcare Ltd
Figure 2. Treat to target approach: algorithm for the management of inflammatory arthritis.
RHEUMATOID ARTHRITIS targets and the importance of distinguishing active disease from established joint damage, the decisions made during the patient’s visit to the clinic are of vital importance. Prescribing anti-inflammatory therapy or giving intramuscular injection of steroids alone without broad consideration of the disease activity status and the treatment targets would have negative implications for the treatment protocol. This would shift the patient’s management style into one-stop service with disease remission being the ultimate goal (El Miedany et al, 2005). Prior to their visit to the clinic, every patient should have blood tests (including tests for full blood count, liver and kidney functions as well as inflammatory markers, e.g. erthyrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) to facilitate DAS measurement. If possible, X-rays or ultrasound scans should be reviewed with the patient on the same day. If this is not possible, they should be reviewed later by the treating physician and therapeutic decisions should be made (El Miedany and Palmer, 2012). Furthermore, the treatment plan should agree on certain points. For example, patients should be reviewed every 3 months, where response to therapy should be assessed with a view to amending the dose or adding another medication, if not to replace the current therapy (Figure 2).
© 2014 MA Healthcare Ltd
Patient-reported outcome measures (PROMs) Recently, the role of PROMs has expanded from the static phase of capturing and measuring outcomes at a single point of time to a more dynamic role. This dynamic role aims to drive improvement, not only in the quality of inflammatory arthritis care, but also in the patient’s reported experience. Therefore, in addition to its value in tailoring treatment targets adapted to the patient’s needs, the use of PROMs also has the potential to modify the disease impact by improving patients’ adherence to therapy and allowing them to monitor changes in their condition (El Miedany et al, 2011). While pain score, patient global assessment and duration of morning stiffness are used as measures of the patient’s health status or health-related quality of life at a single point in time, functional disability assessment plays an important role in the assessment of the disease impact on the patient and, in the meantime, functions as a predictor of disease outcome. A study (Minaur et al, 2004) following 100 RA cases from diagnosis for 40 years or until death, reported that functional disability was significantly (P
Abstract
Integrating the rheumatoid arthritis (RA) treat-to-target concept into standard clinical practice represents a challenge to health professionals. So far, this practice-changing approach has not been widely implemented, in spite of linking its outcome to payment, which was adopted in the best practice tariffs. The recently published revisions in classification criteria and updated recommendations for optimising the use of disease-modifying anti-rheumatic and biologic agents in the treatment of RA paved the way for re-evaluating the standard clinical care models in order to improve patient outcomes, prevent joint damage, and maintain patients’ functional ability as well as their quality of life. This article discusses the recent advances in the management of RA and provides a set of recommendations to provide comprehensive guidance for treatment to target with the aim of improving the quality of care for RA patients. Key words: Treat to target ■ Rheumatoid arthritis ■ Patient-reported outcome measures (PROMs) ■ Patient-reported experience measures (PREMs) ■ Ultrasound
O
ver the past few decades, a revolution has occurred in the management of rheumatoid arthritis (RA), which has completely changed the way RA patients are managed in standard clinical practice. It started with identifying outcome measures and, later, the development of scores to assess RA disease activity reliably. The development of objective tools, such as the American College of Rheumatology (ACR) response criteria (Felson et al, 1993) and the Disease Activity Score (DAS) (van der Heijde et al, 1993), formed the cornerstone for all clinical trials carried out to assess arthritis treatment. The development of a scoring system for the assessment of radiological impact of the disease on the joints, which highlights the importance of disease control (Sharp et al, 1971), was followed by the development of the functional disability score tool Health Assessment Questionnaire (HAQ) in the early 1980s (Fries et al, 1980), which helped to personalise the treatment of the disease and assess its impact on patients’
lives. These tools enabled the evaluation of the standard drug treatments known as disease-modifying anti-rheumatic drugs (DMARDs), which include methotrexate, leflunomide and sulphasalazine, azathioprine, hydroxychloroquine, and gold injections. Subsequently, the outlook for RA treatment has changed and formed a quantum leap over the previously adopted treatment pyramid (Bensen et al, 1997). The introduction of biologic therapy in the late 1990s also enabled the attainment of unprecedented outcomes for patient care (Feldmann and Maini, 2003; Smolen et al, 2003; Aletaha et al, 2005). These three phases led to the biggest change in RA treatment goals and the introduction of the definition of remission, which means real disease control with no pain, stiffness, swelling or joint damage. Hence, the treatment paradigm changed to adopt the ‘treat-to-target’ approach aiming at disease remission (Smolen et al, 2010). The concept of achieving tight control of RA and treating to target entails: ■■ Early diagnosis ■■ Early and progressive treatment ■■ Regular monitoring. This is expected to lead to positive outcomes in a significant number of RA patients who achieve treatment goals of either clinical remission or low levels of disease activity. As adopting such an approach in standard clinical practice has been linked to payments in what is called ‘best practice tariff ’ (Department of Health (DH), 2013), and in view of the traditional pressure in rheumatology outpatient services, rheumatology specialist nurses and middle-grade health professionals are expected to play an important role in executing this treatment approach. This article provides a set of recommendations to provide comprehensive guidance for treatment to target (Figure 1) and help improve the quality of care for RA patients in clinical practice as set out in the Commissioning for Quality in Rheumatoid Arthritis (CQRA) guidelines (National Rheumatoid Arthritis Society, 2012). The consensus finding was evidence-based, obtained from a systematic literature review and the recently published European League Against Rheumatism (EULAR) guidelines, which revealed improved outcomes with strategic therapeutic approaches (Schoels et al, 2010; Smolen et al, 2013).
Accepted for publication: February 2014
This concept of targeted treatment is closely related to the notion of tight control, which is the practice of measuring disease activity at regular intervals of weeks or months, making sure that the target is met, or adjusting the treatment so that it will be met the next time (van den Broek et al,
310
British Journal of Nursing, 2014, Vol 23, No 6
British Journal of Nursing 2014.23:310-315.
© 2014 MA Healthcare Ltd
Treat to target Deborah Palmer is Advanced Nurse Practitioner, North Middlesex University Hospital, London; Yasser El Miedany is Consultant Rheumatologist, Darent Valley Hospital, Dartford
RHEUMATOID ARTHRITIS 2012). In inflammatory arthritis, the target is to achieve disease remission or a low disease activity state.
Challenges and proposed solutions However, in day-to-day practice, trying to adopt this approach, which should be tailored to the patient’s condition, usually comes with challenges, among which the time factor comes first. In the early inflammatory arthritis (EIA) model defined by ‘best practice tariff ’ recommendations, patients referred with suspected EIA should have their first specialist appointment within 3 weeks of their referral date (DH, 2013). Within 6 weeks of referral, diagnostic testing and any necessary clinical reviews should be completed so that by the end of this 6-week period, people who do not have EIA should be discharged back to the care of their GP, and those with EIA should have received their first prescription for disease-modifying therapy. To meet this challenge, a dedicated outpatient service aimed at seeing this group of patients within 3 weeks would need to be set up. In centres where the workload hinders such timed early patient assessment, setting up a dedicated clinic or nurse-led early arthritis service has proved to be workable and successful (El Miedany et al, 2006). Agreeing a referral pathway with the primary care physician for baseline lab investigation prior to the referral would also help in shortening diagnosis time (El Miedany et al, 2005). The second challenge is the pressure of close monitoring of patients diagnosed as having EIA (Figure 2) to assess for their disease activity and response to therapy, especially in the first year of therapy, which obliges senior health decisionmakers to handle the issue with no further increase in the budget. This is best handled through a service working as a multidisciplinary team, where the patients are to be reviewed by the rheumatology nurses, adopting an agreed treatment protocol (El Miedany et al, 2006). Last, the frequency with which RA patients are evaluated for their achievement of target represents a third challenge. Rheumatology nurses play an important role in facing this challenge. However, in most cases, this might be variable as the frequency of evaluation and monitoring of disease activity should ultimately depend on the patient’s level of disease activity; patients with higher disease activity would require more frequent monitoring (El Miedany et al, 2005).
© 2014 MA Healthcare Ltd
Treatment protocol and decision As the RA treatment paradigm has changed to a patientcentred model since the publication of guidelines from the National Institute of Health and Care Excellence (NICE) in 2009, treatment of the disease should be based on a shared decision between patient and rheumatologist with abrogation of inflammation being the most important goal to achieve desired treatment targets. In concordance with NICE guidelines, the EULAR has released updated recommendations (Smolen et al, 2013) for the management of RA. According to this latest guidance, treatment with DMARDs should be initiated as soon as a diagnosis of RA is made, with the aim of reaching a target of remission (DAS282.6–2.6-3.2 - 5.1
Features of Poor Prognosis*
DMARD Combination therapy
DMARD Monotherapy (Methotrexate 20-25mg/wk)
Assess Disease Activity after 3m Moderate or High Activity
Low Disease Activity Up DMARD Monotherapy dose/ Or Combination Therapy
Add or switch DMARD Try new double/ Triple combination
Moderate Disease Activity
Continue if in remission
Continue if in remission
+ Combined with IM/ short term Low/high steroids
Assess Disease Activity after 3m
High Disease Activity: DAS-28 > 5.1 MTX + Anti-TNF: Adalimumab/ Certolizumab / Etanercept / Golimumab / Infliximab or Tocilizumab or Abatacept
High Disease Activity: DAS-28 > 5.1 The patient is intolerant to MTX, or MTX treatment is considered to be inappropriate Anti- TNF: Adalimumab/ertolizumab/ Etanercept or Tocilizumab
Assess After 3m & 6 m
The Biologic has been withdrawn because of an adverse event within first 6 months of treatment
Consider alternative Biologic Therapy
Adequate response to treatment at 6-months (DAS28 score improved by ≥ 1.2): Continue Treatment
Maintain same treatment / adjust DMARDs dose to achieve remission &monitor patient every 6m
No Adequate response to treatment at 6-months (DAS28 score improved by< 1.2)
Consider alternative Biologic inhibitor (Including Rituximab + MTX)
et al, 2005) Therefore, a more appropriate target disease state should be sustained remission (the absence of disease activity and flare over the longest possible period of time). This may be more difficult to achieve as data suggest that approximately half of RA patients in remission may experience a disease flare within 24 months. Flare has been shown to be associated with more radiographic progression when compared with patients in sustained remission (Molenaar et al, 2004) Therefore, in
standard clinical practice, once remission is achieved, the treating health professional needs to be confident that the patient will maintain this state in order to ensure the best possible outcomes.
One-stop service Taking into consideration the rate at which different patients achieve their targets, the speed with which they achieve their
312
British Journal of Nursing, 2014, Vol 23, No 6
British Journal of Nursing 2014.23:310-315.
© 2014 MA Healthcare Ltd
Figure 2. Treat to target approach: algorithm for the management of inflammatory arthritis.
RHEUMATOID ARTHRITIS targets and the importance of distinguishing active disease from established joint damage, the decisions made during the patient’s visit to the clinic are of vital importance. Prescribing anti-inflammatory therapy or giving intramuscular injection of steroids alone without broad consideration of the disease activity status and the treatment targets would have negative implications for the treatment protocol. This would shift the patient’s management style into one-stop service with disease remission being the ultimate goal (El Miedany et al, 2005). Prior to their visit to the clinic, every patient should have blood tests (including tests for full blood count, liver and kidney functions as well as inflammatory markers, e.g. erthyrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) to facilitate DAS measurement. If possible, X-rays or ultrasound scans should be reviewed with the patient on the same day. If this is not possible, they should be reviewed later by the treating physician and therapeutic decisions should be made (El Miedany and Palmer, 2012). Furthermore, the treatment plan should agree on certain points. For example, patients should be reviewed every 3 months, where response to therapy should be assessed with a view to amending the dose or adding another medication, if not to replace the current therapy (Figure 2).
© 2014 MA Healthcare Ltd
Patient-reported outcome measures (PROMs) Recently, the role of PROMs has expanded from the static phase of capturing and measuring outcomes at a single point of time to a more dynamic role. This dynamic role aims to drive improvement, not only in the quality of inflammatory arthritis care, but also in the patient’s reported experience. Therefore, in addition to its value in tailoring treatment targets adapted to the patient’s needs, the use of PROMs also has the potential to modify the disease impact by improving patients’ adherence to therapy and allowing them to monitor changes in their condition (El Miedany et al, 2011). While pain score, patient global assessment and duration of morning stiffness are used as measures of the patient’s health status or health-related quality of life at a single point in time, functional disability assessment plays an important role in the assessment of the disease impact on the patient and, in the meantime, functions as a predictor of disease outcome. A study (Minaur et al, 2004) following 100 RA cases from diagnosis for 40 years or until death, reported that functional disability was significantly (P
