Quality of Life Assessment and Its Relationship with Fatigue Symptom, Demographic and Clinical Factors in Rheumatoid Arthritis Polish Patients

  

    
Variables
    
b*
    
The standard error for b*
    
b
    
The standard error for b
    
p
  
  

    
Model 1 

      R=0.366;    R2=0.134; Corrected. R2=0.113; 

      F(3.124)=6.41;    p<0.0004; Estimated    standard error:34.58*
  
  

    
Hemoglobin (Hgb) [g/dl] 

      C-Reactive Protein (CRP) [mg/l] 

      Rheumatoid Factor (RF) [IU/ml] 
    
-0.118 

      0.259 

      0.121 
    
0.086 

      0.092 

      0.090 
    
-0.591 

      -0.002 

      0.004 
    
1.138 

      0.216 

      0.025 
    
0.1727 

      0.0057 

      0.1805 
  
  

    
R=0.330; R2=0.109; Corrected.    R2=0.102; 

      F(1.126)=15.37; p<0.0001;    Estimated standard error: 34.81**
  
  

    
C-Reactive Protein (CRP) [mg/l] 
    
0.330 
    
0.084 
    
0.776 
    
0.198 
    
0.0001 
  
  

    
Model 2 

      R=0.438;    R2=0.192; Corrected. R2=0.179; 

      F(2.125)=14.84; p<0.0000;    Estimated corrected error: 33.28*
  
  

    
Pharmacological treatment 

      Disease Activity (DAS28) 
    
-0.136 

      0.379 
    
0.084 

      0.084 
    
-12.770 

      15.104 
    
7.859 

      3.338 
    
0.1067 

      0.0000 
  
  

    
R=0.418; R2=0.175; Corrected    R2=0.168; 

      F(1.126)=26.69; p<0.0000;    Estimated standard error: 33.50� **
  
  

    
Disease Activity (DAS28) 
    
0.418 
    
0.081 
    
16.643 
    
3.221 
    
0.0000 
  
  

    
Model 3 

      R=0.584;    R2=0.341; Corrected R2=0.325; 

      F(3.124)=21.38; p<0.0000;    Estimated standard error: 30.17**
  
  

    
Visual Analogue Scale for 

      Pain (VAS) [cm] 

      Morning stiffness [min] 

      Disease Activity (DAS28) 
    
0.354 
      
0.175 

        0.221 
    
0.082 
      
0.082 

        0.081 
    
5.341 
      
0.093 

        8.809 
    
1.244 
      
0.044 

        3.241 
    
0.0000 
      
0.0359 

        0.0075 
  
  

    
* multiple regression; **    progressive multiple-step regression; R—correlation coefficient;    R2—correlation of determination; F—F test statistic; b — regression    coefficient 
  

Table 8: Multiple regression results for AIMS-2 variable and independent variables.

• Model 1 examined the combined effect of hemoglobin, CRP, and RF on quality of life,

• Model 2 examined the regression analysis for pharmacological treatment (biological/conventional drugs) and disease activity (DAS28),

• Model 3 analyzed the effects of pain (VAS), age (in years), morning stiffness, joint tenderness (Ritchie Articular Index), and disease activity (DAS28) on quality of life.

The most significant impact on the quality of life on the AIMS-2 scale was exerted by VAS pain (b*=0.354±0.082), DAS28 disease activity (b*=0.221±0.081), and morning stiffness (b*=0.175±0.082).

Discussion

In Polish and foreign studies, the level of quality of life is examined using various questionnaires, the size of the study groups varies, and multiple factors are conisered (e.g., clinical, demographic, psychosocial, productivity, or fatigue). These analyzes are intended to determine how the quality of life affects patients with RA and what predictors increase or decrease its level, which may translate into treatment modifications or the determination of specific socio-economic assistance.

As authors, we think the most interesting aspect of this article is multiple regression. This analysis is very rarely used to assess the impact of various factors together on the quality of life of patients with RA. In addition, on the basis of progressive stepwise multiple regression, it is theoretically possible to predict what parameters (and precisely their intensity) affect the perceived quality of life. An attempt to answer and indicate which factors together worsen the patient's condition, and thus negatively affect his quality of life, will allow for an appropriate therapeutic approach to the patient, e.g. by changing medications, incorporating additional therapies. This study analyzed almost all clinical factors specific to RA in order to identify which and to what extent negatively affect patients' quality of life.

Relationships and Correlations between Clinical and Demographic Factors and the Level of Quality of Life

In the presented study on the AIMS-2 scale, the lowest quality of life was obtained by patients in the areas of joint pain, walking and bending, and emotional tension. This may result in difficulties in performing everyday activities and professional duties, as well as absenteeism from work or social and cultural life. The highest quality of life was presented in the domains of support from family and friends and self-care. The study’s authors indicated that the quality of life in RA patients correlates with pain, age, morning stiffness, disease activity, CRP levels, and joint tenderness. However, it has nothing to do with demographic factors.

In another study, Baczyk et al. [8] indicated that a better assessment of the quality of life of patients with RA in the AIMS-2 scale depended on the support received from family and friends. In contrast, lower quality of life was related to joint pain, walking, and bending. As in this study, quality of life correlated with pain, morning stiffness, and hand muscle strength but not with joint tenderness. Kaniewska K et al. [6] showed differences in the AIMS-2 scores on the "walking and bending" scale depending on the severity of RA [6].

Moreover, Roma et al. [20], assessing the quality of life of the subjects using the SF-36 scale, also showed that pain significantly impacted the quality of life, followed by general health, vitality, and physical aspects. In contrast, the subjects rated the emotional, social and mental health spheres the best. It was emphasized that categories from the physical domain significantly impacted the quality of life in patients with RA more than in the mental domain. In this study, 99 respondents rated their quality of life as low.

Matcham et al. [21] conducted a meta-analysis of 31 studies on the quality of life in patients with RA (measured with the SF-36 scale). They unequivocally indicated that the disease, RA, has a negative impact on the sense of the quality of life. Their analyses showed that the scientific literature reports that physical determinants have a much more significant impact on the deterioration of the quality of life than mental determinants. Patients presented the lowest quality of life in the areas of role limitation due to physical health and vitality and the highest in the areas of physical functioning and mental health. Correlations between age (the higher the age, the worse the quality of life in the physical aspect), the duration of the disease, and female sex were also indicated, which in the case of the last two determinants was not confirmed in this study [21].

In randomized studies on the impact of pharmacological treatment (with the use of disease-modifying drugs; DMARDs) on the quality of life (SF-36 scale), Gerhold et al. [22] proved that it has a positive impact on the quality of life in contrast to this current study. Azevedo et al. [23] obtained similar results concerning pharmacotherapy with biological drugs.

In the study by Martiniec et al. [24], pain dominated the factors influencing the quality of life, and reducing pain perception resulted in improved in the quality of life. The pain had a negative impact on such domains of quality of life (as measured by the SF-36 scale and the World Health Organization's Quality of Life Questionnaire (WHOQOL), such as social functioning, the general perception of health, and physical functioning. In Kupcewicz et al. [25], pain also had a negative impact on the quality of life.

Abu Al-Fadl et al. [26] assessed the quality of life using the SF-36 scale. They indicated that RA negatively affects the quality of life's physical and psychological domains. Age did not correlate with the quality of life, in contrast to disease activity and gender - women presented a lower quality of life than men.

Kamisoko et al. [27] also confirmed that pain and disease activity decreases the quality of life. DAS28 significantly impacted the subjects' mental state, pain, and overall quality of life. In the Echelle de Mesure de l'Impact de la polyarthrite Rhumatoïde (EMIR), patients presented the lowest quality of life in the areas of pain and mental and the highest in the area of work.

Cruz-Castillo et al. [28] assessed the quality of life using the Spanish version of the Quality of Life Rheumatoid Arthritis (QOL-RA) tool. Patients rated their quality of life as good or moderate. The following determinants impacted the quality of life in Ecuadorian patients - functionality, disease duration, and disease activity. Aspects of support and social life were rated the highest, and pain and nervous tension the lowest.

Kumar et al. [29] found a significant correlation between the quality of life and CRP concentration.

Besides, Goma et al. [30] confirmed in their research on the Egyptian community that the quality of life is affected by pain, physical disability and limitations in this area, anxiety, depression, and social dysfunctions (such as difficult interpersonal contact).

Tanski et al. [31] indicated that patients treated with biological drugs had a lower quality of life than those treated conventionally, and anxiety and depression negatively impacted their quality of life.

In their studies, Besirli et al. [32] proved that the quality of life (in the mental and physical domains of the SF-36 scale) is influenced by disease activity, anxiety, depression, and suicidal thoughts.

McBeth et al. [33], Abu Al-Fadl et al. [26], Kamisoko et al. [27], Cruz-Castillo et al. [28], Conley et al. [34] that demographic factors do not affect the quality of life in patients with RA. Baczyk et al. [8] pointed out that low education (secondary, vocational, and primary) is responsible for the low quality of life in the physical sphere, but not marital status. Lapčevic et al. [35] showed that occupational qualifications impacted the sense of the quality of life; the higher and better qualifications, the better the quality of life of the respondents, and Rosa-Gonçalves et al. [36] that gender and education influenced the quality of life. Zhou et al. [37] analyzed the quality of life using the SF-36 scale. They indicated that physical functioning, in terms of quality of life, is influenced by extra-articular symptoms, joint tenderness, pain, and low income. In contrast, mental functioning is affected by low income, physical work, the number of swollen joints, and marital status.

Relationships and Correlations between Fatigue Factors and the Level of Quality of Life

The analysis showed a positive correlation of moderate strength between the level of fatigue (FACIT-F scale) and the quality of life (AIMS-2 scale). Higher values accompany higher values in the FACIT-F scale in the AIMS-2 scale, which means that people with more severe symptoms of fatigue report worse quality of life. Own research has shown that the quality of life assessed by patients in particular areas coincides with the statistical analysis within the domains positively correlated with the symptom of fatigue, i.e., walking and bending, joint pain, emotional tension level, but also mobility, hand and finger function, arm function, self-care, social activity, mood, and satisfaction.

Chang-Hee Suh et al. [38] analyzed the quality of life of Korean patients with RA in terms of the disease itself, fatigue, depression, social support, and self-efficacy. Their research confirmed that quality of life is significantly related to fatigue. Rodriguez-Muguruza et al. [39] also obtained similar results, indicating a correlation between emotional tension (examined in the AIMS 2 test) and fatigue. Albayrak Gezer et al. [40], Rongen-van Dartel et al. [41], Öncü et al. [42], and Conley et al. [34] showed in their analyzes that fatigue had the most significant impact on functional efficiency. In contrast (as in this study), fatigue did not affect household tasks. The correlation of domains in the AIMS-2 scale with the symptom of fatigue indicates a kind of functional disability (e.g., in the area of mobility, walking, bending, limb function or self-care). Similar results using other scales were obtained by Lee et al. [43], Campbell et al. [44], Diniz et al. [45], Grøn et al. [46], and Lao et al. [47]. Contrary to their research, Lapčevic et al. [35] indicated that fatigue intensifies due to the use of help from third parties and numerous household duties. This discrepancy may be because in the study group analyzed in this study, as many as 118 out of 128 respondents lived with someone, had support in everyday life, and there were no patients dependent on external carers.

Multiple Regressions between Examined Factors and the Level of Quality of Life

Scientific research shows that it is difficult to isolate which factors affect the level of quality of life. It should be noted that clinical determinants may jointly affect the quality of life, lowering the perception of it or not. Regression analysis in the above studies indicated that pain, morning stiffness, disease activity, and CRP level affect the level of quality of life, where the increase in their parameters worsens the perception of quality of life.

In our study, three models of independent variables for the variable quality of life were subjected to multiple regression analysis.

Model 1 examined the combined effect of hemoglobin, CRP, and RF on quality of life. CRP was significant predictor, explaining 10.2% of the variability of the quality of life in the AIMS-2 scale. An increase in CRP concentration by one point reduced the quality of life on the AIMS-2 scale by an average of 0.776±0.198 points.

In model 2, the regression analysis for pharmacological treatment (biological/conventional drugs) and Disease Activity (DAS28) revealed that DAS28 is a significant factor for life quality (AIMS-2). The regression model allows for explaining 16.8% of the variation in life quality on the AIMS-2 scale. An increase in DAS28 disease activity by one point reduced the quality of life in the AIMS-2 scale by an average of 16,643±3,221 points.

Model 3 analyzed the effects of pain (VAS), age (in years), morning stiffness, joint tenderness (Ritchie Articular Index), and Disease Activity (DAS28) on quality of life.

Significant coefficients for quality of life (AIMS-2) were pain (VAS), morning stiffness, and DAS28. The regression model explained 32.5% of the quality of life value variability. An increase in pain perception in the VAS scale by one centimeter creased the score in the AIMS-2 scale (reduced quality of life) by an average of 5.341±1.244 points. An increase in morning stiffness by one minute increased the AIMS-2 score (reduced quality of life) by an average of 0.093±0.044 points. In turn, an increase in DAS28 disease activity by one increased the AIMS-2 score (reduced quality of life) by an average of 8,809±3,241 points.

The most significant impact on the quality of life on the AIMS-2 scale was exerted by VAS pain (b*=0.354±0.082), DAS28 disease activity (b*=0.221±0.081), and morning stiff-ness (b*=0.175±0.082).

Pain, morning stiffness, and grip strength were significant predictors of impact on quality of life also in Baczyk et al. [8]. Besides, Laric et al. [48] indicated that pain intensity, pain catastrophizing, belief in coping with pain, and alexithymia explained 54% of the variance in the physical component of Health-Related Quality of Life (HRQOL) (p<0.001). Bai et al. [49] assessed the quality of life in patients with RA using the SF-36 scale, Word Health Organization Quality of Life-Bref (WHOQOL-BREF), and Quality of Life Instruments for Chronic Diseases-RA (QLICD-RA). They conducted a multiple regression analysis that showed that sleep duration, psychological counseling, and C4 levels affected the quality of life, as assessed on the SF-36 scale. In the same study, information was obtained that the level of IgA and being overweight together affect the assessment of the quality of life in the WHOQOL-BREF scale.

Adequate sleep and psychological help affect the quality of life assessment in the QLICD-RA scale. Rosa-Gonçalves et al. [36] indicated in the multiple regression analysis that pain, disease activity, and education jointly affect the quality of life (measured on the SF-36 scale). Katchamart et al. [50] indicated that among Thai patients with RA, the quality of life was affected jointly by disease activity, functional disability, depression and anxiety, and pain. In Tanski et al. [31], depression was the main predictor negatively affecting the quality of life, especially in the domains of perceiving the quality of life, perceiving health, and physical health (measured in the WHOQOL scale).

In Mandala et al. [51], in a multiple regression analysis, the quality of life was negatively affected by disease activity, functional disability, treatment with disease-modifying drugs, comorbidities, and extra-articular lesions.

These studies also show limitations related to the small size of the study group, the lack of repeated analyzes after changing pharmacological treatment or changes in the disease activity status, and the lack of conclusions in the area of mental condition. This creates opportunities for further research and the concept of improving the quality of life of patients with RA.

The strength of this study was the use of multiple regression analysis to assess the impact of various factors on the quality of life of patients with RA. In addition, based on progressive stepwise multiple regression, it was predicted which parameters (precisely their intensity) affect the perceived quality of life. In this study, almost all clinical factors characteristic of RA were analyzed to determine which ones and to what extent negatively affect patients' quality of life. These findings may allow a better understanding of RA patients’ problems and affect the therapeutic approach.

Conclusion

Based on a progressive stepwise multiple regression, it has been shown that it is possible to predict what parameters affect the intensity of perceived quality of life. These were pain on the VAS scale, disease activity DAS28, morning stiffness, and CRP concentration (increasing their parameters will reduce the perceived quality of life).

Research on the quality of life and its assessment in individual patients is essential for the treatment itself and the patient's approach to their situation. It allows for individualized treatment and cares for the patient, meeting their needs, changing the direction of treatment, or solving problems that adversely affect the therapy process. The disease does not only affect the body but negatively affects the mind, soul, and social and professional relationships. Therefore, assessing the quality of life in patients with RA should be a permanent element of patient care.

Author Statements

Author Contributions

Conceptualization, G.B.; data curation, K.A.K.; formal analysis, K.A.K., and G.B.; investigation, K.A.K.; methodology, K.A.K., and G.B.; writing—original draft, K.A.K., G.B., and D.F; writing—review and editing, K.A.K., G.B. and D.F; supervision, G.B., and D.F. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Poznan University of Medical Sciences, grant number 502-14-04407637-10441.

Institutional Review Board Statement

The study was conducted following the Helsinki Declaration and was approved by the Ethics Committee of the Poznan University of Medical Sciences, registered under reference numbers 46/16 and 564/16.

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data are not publicly available due to data privacy regulations. The data presented in this study are available upon request from the corresponding author.

Acknowledgments

The authors thank all study participants for their voluntary and willing participation in this study. They also thank the doctors from the Rheumatology Ward of the M. Dega Orthopedic and Rehabilitation Clinical Hospital and the Józef Strus Poznan Multidisciplinary City Hospital, who conducted the medical history assessment and physical examination of patients with RA and shared the results with the authors.

Conflicts of Interest

The authors declare no conflict of interest.

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