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| ORIGINAL ARTICLE |
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| Ahead of print publication |
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Assessment of correlation of fatigue in patients of rheumatoid arthritis using bristol rheumatoid arthritis fatigue multidimensional questionnaire score with disease activity – An Indian experience
Harpreet Singh, Kusum Yadav, Ritu Sangwan
Department of Medicine, PGIMS, Rohtak, Haryana, India
| Date of Submission | 01-Sep-2021 |
| Date of Acceptance | 19-Jan-2022 |
| Date of Web Publication | 01-Jul-2022 |
Correspondence Address:
Kusum Yadav,
Department of Medicine, PGIMS, Rohtak, Haryana 123101
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/injr.injr_197_21
Background: Fatigue affects 40%–80% patients of rheumatoid arthritis (RA), impairing their quality of life.
Objectives: The aim of this study was to assess fatigue by means of Bristol RA Fatigue Multidimensional Questionnaire score (BRAF-MDQ) and correlate it with the disease activity of RA patients. One hundred RA patients (as per American College of rheumatology 1987 criteria) having no underlying other chronic disease were evaluated at baseline (M0), 1 month (M1), and 3 months (M3) for fatigue (using BRAF-MDQ) and disease activity Disease Activity Index 28 (DAS-28) and Clinical Disease Activity Index (CDAI). The correlation between fatigue score and disease activity score was evaluated.
Results: Fatigue score (BRAF-MDQ) decreased from 19.28 ± 13.846 at baseline to 17.46 ± 13.56 at M1 and 13.27 ± 11.633 at M3, respectively (P < 0.001). Similarly, there was significant decrease in disease activity of DAS-28 from 4.439 ± 1.41 at baseline to 3.715 ± 1.655 at M1 and 3.668 ± 1.46 at M3; while CDAI reduced from 18.82 ± 14.314 at baseline to 14.16 ± 12.611 at M1 and 11.65 ± 11.769 at M3, respectively (P < 0.001). There was a positive significant correlation (P value < 0.001) between BRAF-MDQ score and DAS-28 score (r = 0.503; 0.687 and 0.680) and CDAI score (r = 0.642,0.728 and 0.732) at baseline, 1 month, and 3 months, respectively. Multivariate analysis showed that CDAI (M0) was a significant factor affecting BRAF-MOQ score at follow-up of 3 months (M3) with beta coefficient of 0.872, P < 0.0001.
Conclusion: The results of the present study indicate that fatigue quantum is related to disease activity and should be evaluated at the time of diagnosis. BRAF-MDQ is a simple, yet effective patient reported outcome questionnaire which assessed the fatigue quantum. Routine assessment of fatigue through BRAF-MDQ along with assessment of disease activity will be a holistic approach in management of RA.
Keywords: Fatigue, fatigue score, patient reported outcome measures, rheumatoid arthritis
How to cite this URL:
Singh H, Yadav K, Sangwan R. Assessment of correlation of fatigue in patients of rheumatoid arthritis using bristol rheumatoid arthritis fatigue multidimensional questionnaire score with disease activity – An Indian experience. Indian J Rheumatol [Epub ahead of print] [cited 2022 Aug 20]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=349450 |
| Introduction | |  |
Rheumatoid arthritis (RA) is a chronic debilitating disorder with consequences like long-term treatment disability of the joints and fatigue.[1],[2],[3],[4] Fatigue occurs not only with respect to restriction in the physical activity but also in the mental activity.[5],[6] The fatigue in cases of RA ranges from 40% to 80%, almost comparable to the fatigue seen in patients with chronic fatigue syndrome.[7],[8],[9]
Fatigue in RA is often multifactorial and prone to worsening by disease-related components, for instance disease duration and activity, functional status, and other comorbid factors such as obesity, hypertension, and diabetes.[3],[4] As fatigue negatively affects life of RA patients, the outcome measures in rheumatology clinical trials group recommend the measurement of fatigue to be included in RA clinical trials.[10]
Recently, there is increased emphasis on evaluating fatigue in clinical practice as well as in trials. In patients with RA, fatigue is directly related to disease activity and this relationship can be assessed by several methods, the multidimensional assessment of fatigue scale, Chronic Illness Therapy-Fatigue, and medical outcomes survey short form-36.[11] However, the specificity of these fell short of being clinically applicable. Thus, the Bristol RA Fatigue Multidimensional Questionnaire (BRAF-MDQ) and Bristol RA Fatigue Numerical Rating Scale (BRAF-NRS) were devised in 2010 to assess fatigue in RA.[12],[13]
BRAF-MDQ assesses fatigue in 4 dimensions (physical, living, cognition, and emotion) separately and additionally to distinguish between fatigue severity, coping, and effect.[14] The BRAF-MDQ consists of mean score (sum of 4 subscores) with total between 0 and 70. The BRAF-MDQ includes 20 items and four subscales of “physical fatigue (0–22) living with fatigue (0–21) cognitive fatigue (0–15) and emotional fatigue (0–12).” A higher score predicts more fatigue. In a review of twelve patients reported outcome measures in fatigue, the multidimensional BRAF-MDQ appears to be the best choice especially for the higher level of fatigue.[15]
On reviewing the literature, there is no study on assessment of fatigue using BRAF-MDQ in RA patients in Indian population. Hence, the present study was planned to assess fatigue using BRAF-MDQ in RA patients and to study its correlation with disease activity.
| Methods | | |
A prospective observational study was done on hundred patients of RA diagnosis based on American College of rheumatology criteria 1987. The patients were enrolled over a period of February 2018 to January 2019 after obtaining a written informed consent and institutional ethical clearance (IEC/TH/17/MED/02, DATED 04.12.17). Excluded patients were the ones who were anemic or had other comorbidities like malignancy, hypothyroidism, renal disease, cardiac disease, liver disease, or pulmonary disease. The enrolled subject was analyzed for complete clinical history, biochemical investigation, and radiographic findings from baseline till the follow-up of 3 months. All the patients were analyzed for the disease activity by using Disease activity score-28 (DAS-28) and Clinical Disease Activity Index (CDAI) score.[16],[17]
The fatigue was assessed using BRAF-MDQ questionnaire. The questionnaire was in English language. The principal investigator explained the questionnaire to the patients and filled their responses in the questionnaire by himself.
Feedback from patients
Initially, some patients were skeptical for getting involved in the study, but after appropriate counseling, most of the patients were compliant till the study completion. BRAF-MDQ questionnaire was found very easy, understandable, and comfortable for the patients.
During the study, all subjects continued with their medications and the aforementioned scores were reassessed at follow-up of 1 month and 3 months. No treatment changes were done during the study period to avoid any confounders.
Statistical analysis
Data were collected and analyzed by using the Chi-square test, repeated measure ANOVA test, and Statistical Package for the social sciences version 20. Pearson correlation coefficients were used to correlate BRAF-MDQ, DAS28, and CDAI score. Cronbach's was used to measure the reliability of BRAF-MDQ, DAS28 score, and CDAI score. Univariate and multivariate linear regression was done to find factors affecting BRAF-MOQ total score at M3. Values were expressed as numbers, percentage, mean ± standard deviation. Statistical significance was measured by P < 0.05 = significant.
| Results | | |
The study comprised 77 females and 23 males with mean age being 42.59 ± 12.76 years. The median age was 40 years in females and 54 years in males. The mean duration of the disease was 5.5 ± 3.6 years. 80% of the patients was literate and 20% were illiterate. Rheumatoid factor seropositivity was seen in 75% cases while 25% cases were seronegative. The mean DAS28 and CDAI score at baseline (M0) were 4.44 ± 1.42 and 18.82 ± 14.31, respectively [Table 1].
Assessment of disease activity
Disease activity of the study group was assessed using BRAF-MDQ, DAS28, and CDAI score at baseline (M0) and at 1 month (M1) and at 3-month follow-up (M3).
Compared to M0, tender joint counts (TJC) were significantly lesser at M1 (1 vs. 2, P < 0.0001) and M3 (1 vs. 2, P < 0.0001); swollen joint counts were significantly lesser at M1 (2 vs. 5.5, P = 0.0003) and M3 (3 vs. 5.5, P = 0.0004); (ESR in mm/1st h) was significantly lesser at M1 (22 vs. 31, P < 0.0001) and M3 (24 vs. 31, P < 0.0001); global assessment was comparable at M1 (20 vs. 30, P = 0.208) and significantly lesser at M3 (10 vs. 30, P < 0.0001); patient global assessment (PGA, mm) was comparable at M1 (5 vs. 5, P = 0.673) and significantly lesser at M3 (2 vs. 5, P < 0.0001); Evaluator global assessment (EGA in cm) was comparable at M1 (2 vs. 3, P = 0.3) and significantly lesser at M3 (1.5 vs. 3, P < 0.0001); DAS 28 score was significantly lesser at M1 (3.64 vs. 4.38, P < 0.0001) and M3 (3.56 vs. 4.38, P < 0.0001); and CDAI score was significantly lesser at M1 (9.5 vs. 16, P = 0.0002) and M3 (8 vs. 16, P < 0.0001) [Table 2]. | Table 2: Comparison of disease activity characteristics of the study between M0, M1 and M3
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Compared to M0, physical score was comparable at M1 (9 vs. 10, P = 0.222) and significantly lower at M3 (7.5 vs. 10, P < 0.0001); living score was comparable at M1 (2.5 vs. 4, P = 0.111) and significantly lower at M3 (2 vs. 4, P < 0.0001); cognition was comparable at M1 (1 vs. 1, P = 0.562) and significantly lower at M3 (0 vs. 1, P = 0.0002); emotion was comparable at M1 (1 vs. 1, P = 0.838) and significantly lower at M3 (0.5 vs. 1, P = 0.003); and BRAF-MOQ total score was comparable at M1 (15.5 vs. 19, P = 0.251) and significantly lower at M3 (10 vs. 19, P < 0.0001) [Table 3]. | Table 3: Comparison of fatigue characteristics of the study between M0, M1, and M3
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BRAF-MOQ total score showed significant positive correlation with DAS28 at M0 (r = 0.495, P <.0001), M1 (r = 0.666, P < 0.0001), and M3 (r = 0.621, P < 0.0001). BRAF-MOQ total score also showed significant positive correlation with CDAI at M0 (r = 0.611, P < 0.0001), M1 (r = 0.712, P < 0.0001), and M3 (r = 0.678, P < 0.0001) [Table 4]. | Table 4: Correlation of Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire total score with Disease activity score-28 and Clinical Disease Activity Index
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On univariate linear regression, CDAI and DAAS28 were significant factors affecting BRAF-MOQ score at follow-up of 3 months (M3) [Table 5]. On multivariate linear regression, only CDAI (M0) was a significant factor affecting BRAF-MOQ score at follow-up of 3 months (M3) with beta coefficient of 0.872, P < 0.0001 [Table 6]. | Table 5: Univariate linear regression to find out factors affecting Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire total score at M3
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 | Table 6: Multivariate linear regression to find out factors affecting Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire total score at M3
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| Discussion | | |
RA is a chronic inflammatory disease. The quality of life of these patients is adversely affected due to multiple reasons, increasing disability and fatigue being the most important detrimental factors. Fatigue is a crucial symptom of any chronic disease, which can be described as extreme exhaustion and insufficient energy. The multifaceted effects of fatigue may lead to psychosocial, emotional, behavioral, and mental consequences.[18],[19] Therefore, fatigue being one of the most important symptoms should be examined as one of the basic outcome measures of RA.[20],[21]
The objective of our study was to evaluate fatigue using BRAF-MDQ and correlate it with the disease activity. The mean value of BRAF-MDQ score was 19.28 ± 13.84; 17.46 ± 13.56 and 13.27 ± 11.63, respectively, at baseline, at 1 month, and at 3 months (the decreasing score suggest a lower fatigue severity) [Table 2]. Likewise, DAS28 scores were 4.439 ± 1.41, 3.715 ± 1.655, and 3.668 ± 1.46 at baseline, 1 month, and 3 months, respectively [Table 1]. Similarly, CDAI scores were 18.82 ± 14.314, 14.16 ± 12.611, and 11.65 ± 11.769 at baseline, 1 month, and 3 months, respectively [Table 1]. Elevation in proinflammatory cytokine level is capable of promoting fatigue in RA.[22] Interleukin-6 is one of the cytokines which plays a significant role in RA pathogenesis and promotion of fatigue.[23],[24] Use of DMARDs in RA decreases the proinflammatory/inflammatory responses. The correlation of fatigue score (BRAF-MDQ) with disease activity score (DAS 28/CDAI) at regular intervals of follow-up using Pearson correlation coefficient was found statistically significant (P < 0.001) [Table 3]. A similar observation was made by Colak et al.[25] However, Moneim et al. did not find the correlation between DAS28 and BRAF-MDQ to be significant.[26] None of the study available till time have studied the correlation between BRAF-MDQ score with disease activity score (DAS28/CDAI) on follow-up.
The correlation of BRAF-MDQ individual variables with disease activity score (DAS 28/CDAI) was observed to be significantly well correlated at baseline, at 1 month, and at 3 months (all P < 0.001) Hewlett et al.[27] showed that disease activity was well correlated with all 4 subscales with correlation coefficient of r = 0.75–0.88. In a study by Colak et al., disease activity was correlated well with all subscales of BRAF-MDQ score except emotional subscales.[25]
The individual core variables of disease activity score (DAS 28/CDAI score-SJC, TJC, ESR, GH, PGA, and EGA) also correlated well with BRAF-MDQ fatigue scale (P < 0.001) and on regression analysis, CDAI showed a significant risk factor association. Unlike the present study, none of the studies had analyzed the individual disease activity core variables with BRAF-MDQ except for Moneim et al. who found a significant correlation between BRAF-MDQ and ESR (the only core variable studied in their study).[26]
| Conclusion | | |
The results of the present study indicate that fatigue quantum is related to disease activity and should be evaluated at the time of diagnosis. BRAF-MDQ is a simple yet effective patient-reported outcome questionnaire which assessed the fatigue quantum. Routine assessment of fatigue through BRAF-MDQ along with assessment of disease activity will be a holistic approach in the management of RA.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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