2MD, Rheumatology & Rehab, Ain Shams University, School of Medicine St. Abbassia, 11381, Cairo, Egypt
3MD, Community and Public Health, Ain Shams University, School of Medicine St. Abbassia, 11381 Cairo, Egypt
Methods: Early RA patients diagnosed according to ACR/EULAR criteria were treated according a treat-to-target regime with regular disease activity monitoring. Remission was measured as: 1) patient perceived-; and 2) Physician perceived-remission. The study included 188 RA patients and 87 rheumatologists. All participants were asked to complete a survey composed of all domains identified in relation to the disease remission. 10 cm visual analogue scale was used to illustrate the importance of each domain.
Results: The top 4 domains reported in the patients’ cohort who achieved remission were: pain (76%), functional ability (71%), quality of life (69%) and fatigue (43%), whereas the top 4 in the rheumatologist cohort were: low disease activity score (88%), radiologic remission and progression of erosions (76%), lab measures (ESR, CRP) (57%) followed by work difficulties (49%). There was a dynamic pattern of the most important domains reported when patients are stratified according to age, disease duration, comorbidity and motivation.
Conclusion: Different factors are important for rheumatologists and RA patients regarding disease remission. Treatment satisfaction is determined not only by disease activity indices but also by other patient-oriented factors. PROMs could optimise targeted therapy as it can play a significant role in identifying disease activity parameters relevant to both the treating rheumatologist as well as the patient.
Keywords: Discordance; PROMs; Rheumatoid arthritis; Patient perceived remission; Physician perceived remission
In contrast to many chronic diseases, where a single “gold standard” measure, such as blood pressure in hypertension, haemoglobin A1C in diabetes, and lipid profile in hyperlipidemia etc., is applicable to diagnosis, management, prognosis, and analyses of outcomes in all individual patients in clinical trials, clinical care, and long-term databases; in inflammatory arthritic conditions (excluding gouty arthritis), there is not a single “gold standard” measure to assess outcomes. This is applicable both in short-term trials such as joint and laboratory measures, as well as in long-term studies such as radiographic progression, disability, and death. The absence of such a gold standard measure highlighted the need for pooled indices as a valid tool [14, 15]. However, the most commonly used tools to monitor disease activity and identify remission do not endorse the concept of patient reported remission satisfactorily. For example, disease activity score (DAS-28) [16] includes only patient global assessment in addition to tender and swollen joints as well as inflammatory marker measure. Similarly, the ACR/ EULAR remission definition [17] included only patient global assessment, based on the strong correlation between patient global assessment and pain. Furthermore, apart from physical functioning, no other patient reported outcome was available in the validation phase of this definition.
There is a current need to evaluate the patients’ perspective of disease remission and how and which aspects of disease activity measures are most profound to them. There is also a need for further information regarding the performance of variable combinations of patient reported outcomes in relation to remission in RA. Since remission is relatively a new treatment target, and knowledge on the patients’ perspective on remission is limited, there is requirement for identifying specific and sensitive outcome measures for remission in RA patients. This study was carried out aiming at: 1. Identify whether there is a discordance on comparing the patient versus the rheumatologist perspective on remission in RA; and, 2. Determine, from the patient perspective, the relation of patient reported outcomes to the most prevalent specific disease aspects reported in RA patients who achieved remission.
At baseline and after 12, 24, 36 and 52 weeks of treatment PROMs as well as Disease Activity score (DAS-28) were assessed and recorded.
Patients who achieved remission and remained in remission for 6-months (sustained remission), were included in this work.
2. Physician perceived remission was defined as a physician global assessment ≤1 on a visual analogue scale (0-10 VAS), phrased: “How active do you think the rheumatoid arthritis of your patient is today?”
3. ACR/EULAR Boolean-based definition of remission [17] with swollen joint count, tender joint count, patient global assessment as well as CRP all ≤1.
4. DAS-28 score < 2.6 and CDAI < 2.8 (CDAI=swollen joint count + tender joint count + physician global assessment + patient global assessment)
All patients who achieved remission and included in this study, met these 5 criteria.
The survey was completed by 188 RA patients who were in remission, as well as 188 RA whose disease remained active (DAS-28 >3.2). 61-rheumatologists were also asked to complete the RA remission questionnaire, from their perspectives.
Parameter |
Study Group (188 patients) |
Control group (118 patients) |
Male: Female |
76:112 |
75:113 |
Age (Mean±S.D) years |
52.4 ± 11.7 |
53.1 ± 10.4 |
Disease duration (Mean±S.D) months |
19.3 ± 8.9 |
19.5 ± 9.1 |
DAS-28 score(Mean±S.D) |
1.7 ± 0.6 |
4.8 ± 4.2 |
Duration of morning stiffness (Mean±S.D) minutes |
5.2 ± 3.7 |
42 ± 76 |
Functional Disability (score 0-3) |
0.1±0.3 |
1.1 ± 0.8 |
Quality of life (score 0-3)(Mean±S.D) |
0.1 ± 0.2 |
1.2 ± 0.9 |
Patient Global score (VAS 0-10) (Mean±S.D) |
0.6 ± 0.3 |
5.3 ± 1.4 |
Physician Global score (VAS 0-10)(Mean±S.D) |
0.5 ± 0.3 |
5.9 ± 1.6 |
ESR(Mean±S.D)mm/hr |
8.2 ± 2.6 |
31.6 ± 14.3 |
CRP(Mean±S.D)mg/L |
1.7 ± 2.5 |
19.8 ± 9.7 |
Rheumatoid factor (%) |
151/188 (80.3%) |
153/188 (81.4%) |
Anti-CCP (%) |
124/188 (66%) |
123/188 (65.4%) |
Number of patients on DMARDs (%) |
139/188 (74%) |
138/188 (73.4%) |
Number of patients on biologics (%) |
49/188 (26%) |
50/188 (26.6%) |
Age: Cut-off point 65-years old.
Patients < 65 scored functional ability significantly higher than those >65 years of age (9.3 Vs 8.1 on VAS, p=0.03). Similarly work ability was scored higher in the patients below 65 than those above 65 (8.8 Vs 5.1 on VAS, p< 0.05)
Patient’s cohort >65 years of age, rated quality of life at a higher level (9.4 Vs 8.4) than those < 65 years old. Likewise, independence was rated higher in the cohort of patients>65 years old (8.4 Vs 6.7 on VAS, p< 0.05)
There was no significant difference in pain and fatigue scores between patients’ cohorts classified by age.
Disease duration: Cut off point 2-years
Mean level of importance scores of functional ability (9.3 Vs 8.6) and independence (9.1 Vs 8.1) were significantly higher in patients with longer-standing disease (>2-years) as compared to patients with shorter disease duration (< 2-years) (p< 0.05),
Patients with low Motivation rated high: Depression, anxiety, support, independence, ability to work, functional ability
Ability to work, feel normal and ability to socialize were all rated higher in the cohort of patients whose arthritis is in deep remission in contrast to those who were in sustained remission (mean scores were 9.3 Vs 8.8, 9.6 Vs 9.1 and 8.9 Vs 8.1 respectively).
Table 2 shows the discordance of the top rated 3 domains and its scores amongst the RA patients included in this study, who achieved remission, when stratified according to the commonest variables. [Table 2]
|
Age (years) |
Disease Duration (years) |
Disease activity (DAS-28_ |
Comorbidity |
Motivation (score out of 10) |
|||||
Stratification |
<65 |
>65 |
>2-yr |
<2-yr |
<2 |
2-2.6 |
<2 |
>3 |
<1 |
>6 |
|
Fn. Ability |
QoL |
Fn. Ability |
QoL |
Ability to work |
Independence |
Independence |
QoL |
Independence |
Depression |
|
9.4 ± 0.2 |
9.4 ± 0.3 |
9.3 ± 0.3 |
8.9 ± 0.4 |
9.3 ± 0.3 |
9.2 ± 0.3 |
9.1 ± 0.4 |
9.4 ± 0.3 |
9.5 ± 0.3 |
9.6 ± 0.3 |
|
Work ability |
Independence |
Independence |
Work ability |
Feel normal |
Stiffness |
Socialize |
ADL |
Fn Ability |
Anxiety |
|
8.8 ± 0.4 |
8.4 ± 0.3 |
9.1 ± 0.3 |
8.7 ± 0.5 |
9.1 ± 0.4 |
8.9 ± 0.4 |
9.1 ± 0.3 |
9.2 ± 0.2 |
9.1 ± 0.3 |
9.5 ± 0.4 |
|
Socialize |
Family role |
Stiffness |
Feel normal |
Socialize |
ADL |
Family Role |
Anxious |
Work ability |
ADL |
|
8.7 ± 0.4 |
8.6 ± 0.5 |
8.7 ± 0.6 |
8.7 ± 0.5 |
8.9 ± 0.5 |
8.8 ± 0.6 |
8.9 ± 0.5 |
8.9 ± 0.5 |
8.9 ± 0.3 |
9.3 ± 0.3 |
Multivariate Logistic regression |
OR to achieve PtGA<1 |
95% CI |
HAQ improvement in first 3month* |
3.5 |
13-Jan |
Patient motivation improvement in the first 6-months* |
2.9 |
1.2-6.5 |
QoL improvement in first 3month* |
2.8 |
1.4 – 4.6 |
MS improvement in the first 6month* |
1.9 |
1.1+-2.7 |
Fatigue score improvement in the first 6 months* |
1.8 |
2.2-7.4 |
HAQ: Health Assessment Questionnaire, QoL: Quality of Life, MS: Morning Stiffness
The multivariable linear regression showed that significant improvement (>50%) of functional disability, motivation, quality of life and fatigue were independent predictors of disease activity remission as well as patient reported global score< 1. [Table 3]
Results of this study revealed discrepancies in the patients’ perspective, in comparison to the Rheumatologists’ perception, of evaluating their disease activity status and identifying the main themes of rheumatoid arthritis remission. There were also discrepancies amongst RA patients themselves, comparing those who achieved remission to those who have not. These findings agree with earlier published data[25]reporting that whilst ‘Staying independent’, ‘reducing pain’, and ‘keeping mobile’ were the most frequently selected by RA patients who achieved remission as the top 3 (by 39%, 36% and 34% respectively)and are already in the American College of Rheumatology (ACR) core set; others such as ‘returning to/ maintaining a normal lifestyle’, ‘feeling well in myself’ and ‘enjoying my life’ which were also commonly selected (by 26%, 20%and 18% respectively), are not in the ACR core set or disease activity score (DAS). In another study [26], the “RA Impact of Disease (RAID) index”, a patient-derived composite response index developed by a EULAR initiative, pain(21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%),coping (12%), and physical well-being (12%) [12] Were identified by the patients as the most important domains expressing their concept of remission. In a third study [27], outcomes revealed that the discordance between patient’s and evaluator’s assessment of disease activity may reduce the likelihood of remission across the RA and PsA diagnoses as well as across different treatment regimens. These data suggest that patient priorities only partly overlap with those included in the core sets developed by health professionals. It also highlights the importance of including domains identified by the patients, representing their disease activity status, as part of the standard clinical practice. In addition to its role in the patient management, this will also improve communication and establish a real doctorpatient partnership towards successful management.
The dynamic nature of the domains rated by RA patient who achieved remission, identified in this study, endorse the importance of consistent recording and monitoring of these measures on regular basis during the patient’s management course. Results of this study agree with the earlier study done by van Tuyl et al [28] where some differences were reported between different patient groups when stratified for age, gender, disease duration, the presence of comorbidities and joint damage. Whilst performing one’s family role was more relevant and reported imported amongst younger patients, older patients rated functional ability and feeling independent of higher importance. In concordance, outcomes of this work revealed that functional ability was rated higher in patients with longer-standing disease as compared to patients with shorter disease duration, whereas patients with low motivation rated depression, anxiety, support, independence, ability to work, functional ability as the highest. These findings come in concordance with earlier published data which reported that whilst most available analysis of patientphysician discordance identified pain, physical function and health-related quality of life as potential predictive factors of discordance, in RA; psychological aspects and to a lesser degree, fatigue, remain rarely reported in clinical trials and cohorts of RA patients [29]. This was supported by the outcomes of another study [30] which attributed that discordance between patients and their treating physicians, to psychological factors rather than physical domains of health amongst RA patients. The study reported that depression was found to be associated with an underestimation by the physician of the patient’s symptoms (i.e., pain, anxiety, physical function). Outcomes of this work revealed that the patient’s motivation seems to be important, however, this has been overlooked in earlier studies. These findings ratify the importance of considering these measures whilst assessing and managing the patients in the day to day clinical practice. Disagreements in the assessment of the disease activity status are a real problem, with an impact on treatment decisions and treatment outcomes. Regular scoring would be of vital help to identify any significant changes in these domains.
Identifying the most important domains representing the patients’ perspective of remission won’t be meaningful without a tool to assess and monitor them. Such tools recording the patients’ input, should be reproducible, reliable and sensitive to change. Results of this work revealed that PROMs could fill this gap in the patients’ management. In comparison to the patients not in self-perceived remission, those in self-perceived remission had significantly improved changes in functional disability, quality of life, fatigue as well as patient motivation scores. PROMs offer the potential to expand the disease activity/ remission core set in standard clinical practice, as well as longitudinal observational studies, improving the incorporation of the patient perspective, and including disease impacts such as fatigue and patient motivation as a core criterion. The dynamic nature of PROMs has been depicted in earlier study [31]. Results of that work revealed that the dynamic role helps in driving improvement not only in the quality of inflammatory arthritis care but also in the patients’ reported experience. Therefore, in addition to its value in tailoring treatment targets adapted to the patient’s needs, PROMs also have the potential of modifying the disease impact through improving the patients’ adherence to therapy and allowing the patients to monitor the changes in their condition.
PROMs enabled the patient and the treating physician identifies the aspects of relevance necessary for optimal clinical management. Treatment strategies aiming at remission should consider the patient perceived remission in their pathway. Discordance may hamper shared decision-making.
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