Rheumatoid arthritis is an autoimmune disorder characterized mainly by targeting the joints leading to arthritis, limitation, deformities and even joint destruction. Joint affection may interfere with patients’ occupational, vocational and recreational activities leading to a very miserable life in some cases.

Early diagnosis and treatment of rheumatoid arthritis aimed mainly to limit attacks of arthritis to protect the joint from losing its function and integrity. Various medications have been and still are being introduced to the market aiming to prevent the burden of disability on patients, caregivers and communities.

Disease-modifying anti-rheumatic drugs have been found to reduce functional disability for at least 1 or 2 years1–6 while delay in the use of these drugs proved to result in worse outcomes.7–10 Moreover, many reports suggested that there have been major modifications in DMARDS’ treatment strategies throughout many years that were found to improve long-term outcomes.11–13 A recent article by Gwinnutt et al. published in 2017 stated that according to a 20-year follow-up of patients included in the Norfolk Arthritis Register, early treatment of RA leads to improved long-term functional outcomes compared with later treatment (>6 months after symptom onset).14

In 2008, Oken et al. studied factors associated with functional disability and found that between all studied factors only disease activity had an impact on physical function as every small improvement in disease activity scores resulted in a large gain in activities of daily living and that treatment should mainly target disease activity.15

In 2015, the concept of disability determinants began to change again. Even in the era of biologic therapy, the effect of other possible factors not related to therapeutic strategies was studied. Female sex, corticosteroids, and antidepressants were described as profound determinants of disability.16

Later in June 2016, a group of researchers developed a clinical prediction tool for estimation of disability at 1 year with scores ranging from 0 to 26. Higher scores corresponded with higher probabilities of reporting higher HAQ scores at 1 year. The tool contained anxiety and depression scores, employment, absenteeism and BMI.17 In 2017, Ji et al. studied disability and quality of life in 101 Chinese RA patients, they found that long disease duration, high disease activity, a larger number of tender and swollen joints, and high C-reactive protein (CRP) level were all associated with functional disability and added that participants with functional disability tended to have more severe depressive symptoms and a lower quality of life.18

Despite the introduction of more advanced technologies in drug manufacturing and the great improvement in disease outcome; minimizing disability and enhancing physical function to its optimal levels is still a challenge. The control of inflammation does not seem to be the only approach anymore; a more comprehensive approach may be needed to optimize physical function based on understanding the role of all underlying mechanisms and factors.

As is the case for any disease, factors influencing its outcome differ from one population to the other. Researchers in different parts of the world work hard to study different populations to determine the determinants of disease outcome in each. From this point of view our aim was to study an Egyptian population with RA detecting different determinants and contributing factors of functional disability and higher MHAQ scores seeking to target these factors in the future to improve patients overall physical activity and functional outcomes.

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained from all individual participants included in the study.

Rheumatoid arthritis outcome differs greatly between populations and individuals. Decreased physical function and disability are most problematic being a disease mainly targeting joints. Disease activity has been thought to be the main contributor to disability, but other factors are still being highlighted in more recent studies and in different populations. In this study we gathered patients from Rheumatology departments of two Egyptian university hospitals aiming to identify determinants of disability and high MHAQ scores in these patients.

Regarding patients’ demographics, in our study age correlated significantly with MHAQ scores while no significant difference was found between males and females. Aging is well related to disability as shown in other studies24–26 usually due to longer disease duration, longer exposure to medications, more co-morbidities, general debility, polypharmacy with more drug interactions and refusal of medications. Patients between 40 and 60 years of age had the highest MHAQs moreover those with disease duration greater than 10 years showed greater disability. In other populations, female sex was found to be associated with greater disability.16 Patients’ height, weight and BMI were not determinants of MHAQ scores in this studied group.

Not surprisingly nearly all parameters of disease activity including morning stiffness, Physician's Global VAS, General Health, TJC, SJC, ESR, and DAS 28 showed significant positive correlation with MHAQ scores. In multiple regression analysis tender joint count showed the highest influence on MHAQ denoting the importance of controlling activity in RA patients as a mainstay in improving patients’ wellbeing. Erosions in X-rays and subluxations detected either clinically or radiologically contributed to higher MHAQ as indicators of joint destruction and dysfunction. So in other words the actual presence of erosions and sublaxations was more associated with disability rather than just seropositivity. These findings were partly different from the results of Krause et al. who found that RF status, inflammatory markers, and joint erosions were not associated in univariate analysis to disability.16 While in many other previous cohort data multiple clinical factors were associated with disability including tender joint count, inflammatory markers including ESR and CRP, and joint damage.24–27

Among all co-morbidities a higher MHAQ was found in patients with ischemic heart disease compared to those without and the difference was statistically significant. RA increases the risk of ischemic heart disease as a chronic inflammatory disease with elevated CRP enhancing atherosclerosis in addition to the burden of corticosteroid use. Ischemic heart disease seemed to interfere with activities of daily livings raising MHAQ scores in such patients.

Psychosocial factors were found to further modify these clinical factors and contribute to the different disease outcomes.28,29 Depression seemed to interfere with activities of daily living and contributed significantly to disability as MHAQ scores were higher in depressed patients compared to those who were borderline and those who were normal. Moreover, MHAQ scores were correlated with depression scores. This was similar to the results of Ji et al. in 2017 who found that participants with disability had more depressive symptoms.18 Surprisingly, on the other hand no significant difference was found between those actually receiving antidepressants and those who were not, although antidepressants use was found to be one of the determinants of disability in other studies.16 This may be explained by the presence of a group of patients who were undiagnosed and not receiving medications. Interestingly, fibromyalgia was not associated with disability as previously demonstrated in other studies.30 Also patients using anxiolytics showed no higher MHAQS than those not. Some studies also demonstrated similar results showing no relation between fibromyalgia and disability in RA patients.16

Illiteracy is still a major problem in developing countries one of the factors that may not be a great concern in other populations. Illiteracy accounted significantly for higher MHAQ scores showing a highly significant difference between MHAQ scores in illiterate and educated patients with different levels of education. Illiteracy is usually associated with lower adherence to medical care and treatment, less understanding of the disease nature in addition to low socioeconomic level and poverty hindering the compliance with medications and the use of more recent and expensive therapies like biologics.

Although it is widely known that disability rates in the biologic era are declining due to better control of inflammation, this is not a rule in all populations and in fact disability still has an impact on many patients.31 The availability of biologics and its optimal use in clinical practice is still an issue. Limitations in our study were that although we are in the era of biologics only 2 patients in our studied sample received biological therapy which is due to financial causes, so we were limited to demonstrate the value of biological therapy in reducing disability in this studied sample. Conventional DMARDS still provide promising results in many RA patients reducing the urge to use expensive biologics.

Reducing disability and improving the quality of life in rheumatoid arthritis patients is still one of the main goals of therapy. It is necessary to determine the main determinants of disability in each population highlighting those that are modifiable or preventable. In our studied sample of Egyptian Caucasians; aging, illiteracy, disease activity, erosions, subluxations, depression and ischemic heart disease were all related to higher disability. It seems promising that many of these are modifiable if properly addressed by physicians. Disease activity being the main factor causing disability should be controlled which in turn reduces erosions and subluxations. Screening for depression and proper use of anti-depressants is of great value in enhancing patient's coping with RA disease. Proper screening and prophylaxis against ischemic heart disease is mandatory. Finally, rheumatologists should work in collaboration with psychologists, cardiologists and other specialties whenever needed.

The authors declare no conflict of interests