Number№82 (4) 2020

EFFECT OF FIBROMYALGIA ON HEALTH STATUS OF PATIENTS WITH RHEUMATOID ARTHRITIS ACCORDING TO RAID QUESTIONNAIRE

Shevchuk S.V.1, Segeda I.S.2, Shkarivskyi Y.L.1, Khomenko V.M.1

Summary. Background. In patients with rheumatoid arthritis (RA) along with joint pain, often present a neuropathic or diffuse muscular pain, associated with the phenomenon of central sensitization. According to various reports, from 6 to 48% of RA patients have concomitant diffuse muscle pain, sleep impairment and fatigue which is associated with concomitant fibromyalgia (FM). FM significantly modifies the course of RA, so adequate control of the autoimmune inflammatory process in the synovial joints does not always provide effective control of pain. The aim of study was to evaluate the effect of FM on health status of patients with RA according to RAID questionnaire. Materials and methods. In the study were enrolled 63 patients with RA (87.3% female) aged 50.0 [42; 55] years, with moderate and high disease activity (DAS28 >3.2). RA was diagnosed by ACR/EULAR criteria (2010). All patients were on a stable dose of oral NSAIDs and glucocorticoids ≤10 mg/day by prednisolone during the past 4 weeks before the enrollment and did not change doses during the study. The presence of concomitant FM was established by the mACR 2010. The impact of the disease on the patient’s general condition was determined by the RAID (version — Ukrainian for Ukraine). The study was conducted in compliance with bioethical standards. Statistical processing of the results was performed in SPSS Statistics 22.0. Results. Among enrolled patients prevailed seropositive patients by RF 41 (65.1%) and/or by ACCP — 43 (68.3%). In 51 (81.0%) RA patients was detected II–III radiographic stage of joint damage, and 53 (84.1%) patients had the II–III functional class. Extra articular manifestations were found in 16 (25.4%) patients. Among enrolled subjects, 25 (39.7%) RA patients appeared to have generalized pain syndrome, complaints of constant fatigue, sleep disturbances, and psycho-emotional disorders during the past 3 months. According to the mACR2010 criteria, in these patients FM was diagnosed. In RA patients with comorbid FM, RAID indexes were higher (by 15–20%), which significantly associated with markers of the disease activity — the number of tender and swollen joints, DAS28-ESR, HAQ (r>0.6, p<0.01) and ESR, CRP (r=0.4, p<0.05). Results of the re-questioning of patients (RAID-retest) which was performed after 6 days, were similar in patients with RA and RA + FM. Conclusion. Comorbid FM increases impact on the health status of patients with RA, and RAID questionnaire is a simple and sensitive tool for evaluation additional negative influence of FM on RA patients.

УДК: 616.74-009.7:616.72-002.77-052

DOI: 10.32471/rheumatology.2707-6970.80.15190

Rheumatoid arthritis (RA) remains one of the unresolved problems of modern rheumatology due to its high prevalence in the population, rapid disabling of patients. In RA patients along with joint pain, which is associated with the inflammatory process in the synovium and surrounding joint tissues, often present a neuropathic or diffuse muscular pain, associated with the phenomenon of central sensitization [3, 5, 7]. According to various reports, from 6 to 48% of RA patients have concomitant diffuse muscle pain, sleep impairment and fatigue which is associated with concomitant fibromyalgia (FM) [3, 5, 7]. FM significantly modifies the course of RA, so adequate control of the autoimmune inflammatory process in the synovial joints does not always provide effective control of pain [6]. Therefore, objectifying the assessment of the health status of RA patients with comorbid FM is an extremely important task for rheumatology. In 2011, a European League Against Rheumatism (EULAR) initiative created the Rheumatoid Arthritis Impact of Disease (RAID) test to evaluate the impact of the disease on the condition of a patient with RA [1]. The validity of the RAID trial was confirmed by the results of multi-center studies conducted in European countries [2, 8]. The RAID questionnaire consists of 7 scales, according to which the patient independently characterizes the symptoms of the disease and the indicators of the quality of life. In 2019, M.A. Stanislavchuk, K.O. Zaichko (2019) performed a cross-cultural adaptation and validation of the Ukrainian version of RAID questionary in RA patients [9]. The experience of using RAID in trials in patients with RA and concomitant FM is extremely limited [4], so appropriate research is needed.

The aim of study was to evaluate the effect of FM on health status of patients with RA according to RAID questionnaire.

Materials and methods

Inclusion/exclusion criteria

In the study were enrolled 63 RA patients (87.3% women) aged 50.0 [42; 55] years, with moderate and high disease activity (DAS28 >3.2), and disease duration 84 [48; 120] months. The diagnosis of RA was established by ACR/EULAR criteria (2010). The study involved patients with RA duration greater than 6 months, with tender and swollen joints >3, with disease activity by DAS28-ESR >3.2, which had been receiving methotrexate 10–15 mg/week in stable dose for at least 12 weeks. All patients were on a stable dose of oral NSAIDs and glucocorticoids ≤10 mg/day by prednisolone during the past 4 weeks before the enrollment and did not change doses during the study. Patients who were treated with intra-articular injections for the last 4 weeks (for ex. glucocorticoids) and on biologic therapy were not allowed in the study.

Bioethic

The study was conducted in compliance with bioethic norms according to the Declaration of Helsinki «Ethical Principles for Medical Research with Human Involvement as a Object of Study» approved by the 18th General Assembly of the World Medical Association (Helsinki, 1964) with subsequent revisions, the Council of Europe Convention and the Convention biomedicine (1977), relevant provisions of WHO and the laws of Ukraine. All patients signed informed consent.

Patients

Early RA (up to 2 years) was diagnosed in 10 (15.9%) patients, among enrolled patients prevailed seropositive patients by RF 41 (65.1%) and/or by ACCP — 43 (68.3%). In 51 (81.0%) RA patients was detected II–III radiographic stage of joint damage, and 53 (84.1%) patients had the II–III functional class. Extra articular manifestations were found in 16 (25.4%) patients.

All RA patients were evaluated by the number of tender and swollen joints (NTJ and NSJ), RA activity was established by DAS28-ESR and DAS28-CRP, functional disability — by HAQ index.

FM was diagnosed according to the mACR 2010 criteria [10]. Concomitant FM was diagnosed in 25 (39.7%) RA patients.

The effect of the disease on the general condition of the patient was evaluated by RAID (Rheumatoid Arthritis Impact of Disease) questionary, Ukrainian for Ukraine version [9]. Patients completed a self-administered questionnaire within 5 minutes, which included a score of 7 scales (Pain; Functional assessment of performance impairment; Fatigue; Sleep; Physical well-being; Emotional well-being; Adaptation to the manifestations of the disease) in scores from 0 to 10. The final RAID value was calculated metrics calculated for each scale. A RAID index of less than 4 points corresponds to low impact of RA, 4 to 6 points — moderate impact and above 6 points — high impact of RA. Re-questioning of patients (RAID-retest) was performed after 6 days.

Statistic

Statistical processing in IBM Statistics SPSS 22. The significance of the differences was assessed using the Mann — Whitney U-test. Median, first to third quartiles interval, 25–75% percentile were determined. The normality distribution was evaluated by the Shapiro-Wilk test. Non-parametric Spearman correlation analysis was used to evaluate the relationship between the indicators. The critical level of difference of significance for statistical hypotheses testing was considered p<0.05.

Results

Among enrolled subjects, 25 (39.7%) RA patients appeared to have generalized pain syndrome, complaints of constant fatigue, sleep disturbances, unrestored sleep, frequent headache, depressed mood, impaired attention, emotional disorders. According to the mACR2010 criteria, these patients were diagnosed with FM.

Groups of patients with RA and RA + FM did not differ in age and sex distribution, duration ofunderlying disease, frequency of seropositivity by RF and/or ACCP, radiological stage and extra articular manifestations (Table 1). However, RA + FM patients had significantly higher NTJ (50%), higher DAS28-ESR and HAQ (12.9 and 16.6%) compared to RA patients. Among patients with RA + FM, the proportion of persons with high disease activity (DAS28-ESR >5.1) was 1.6 times higher than among RA patients. Meanwhile, no significant differences were found between patients with RA and RA + FM by laboratory markers of the inflammatory process (ESR, CRP) and NSJ.

Table 1. Clinical and demographic characteristic of patients (n=63)

Characteristic RA (n=38) RA + FM (n=25) р
Female n (%) 33 (86.8%) 22 (88%) >0.05
Male n (%) 5 (13.2%) 3 (12.0%) >0.05
Age, years Ме [Р25; Р75] 50 [42; 53] 49 [42; 58] >0.05
Duration of RA, month. Ме [Р25; Р75] 84 [39; 120] 72 [48; 120] >0.05
Sero (+) by RF n (%) 27 (71,7%) 14 (56,0%) >0.05
Sero (+) by ACCP n (%) 28 (73,7%) 15 (60,0%) >0.05
X-ray stage ІІ — ІІІ n (%) 32 (84.2%) 19 (76.0%) >0.05
Limitation of joints function n (%) 36 (87.3%) 17 (68.0%) >0.05
Extra articular manifestations n (%) 10 (26,3%) 6 (24,0%) >0.05
NTJ Ме [Р25; Р75] 8 [7.0; 10.0] 12 [10.0; 14.0] <0,01
NSJ Ме [Р25; Р75] 6.0 [4.0; 8.0] 4.0 [3.0; 7.0] >0.05
ESR, mm/h Ме [Р25; Р75] 32.5 [23.3; 40.0] 28 [18.0; 38.0] >0.05
CRP, ml/l Ме [Р25; Р75] 18.0 [7.6; 18.0] 14,2 [6,0; 18,0] >0.05
DAS28-ESR Ме [Р25; Р75] 5.02 [4.86; 5.54] 5.67 [5.4; 6.10] <0.05
DAS28 >5,1 n (%) 18 (47,4%) 20 (76.0%) <0.05
HAQ Ме [Р25; Р75] 1.50 [1.25; 1.75] 1.75 [1.50; 2.13] <0,05
Tender points FM Ме [Р2575] 6.0 [6.0; 7.0] 14 [12.0;15.0] <0.001
Scale FM Ме [Р2575] 9.0 [8.0; 10] 18 [15.0; 19.0] <0.001
Scale FM ≥13 n (%) 0 (0.0%) 25 (100%) <0.0001

The evaluation of the RAID index scales and their specific contributions showed significant differences between RA patients depending on the comorbidity with FM (Table 2). In the presence of FM in RA patients, significantly higher rates of pain, fatigue and sleep disturbances were recorded, but significantly lower rates of functional activity and physical well-being than in RA patients without FM. There were no significant differences in the emotional well-being and adaptation to the disease. It should be noted that the most significant differences between RA and RA + FM patients were recorded on the scales with the highest specific contribution to the RAID index. Overall, the final RAID index in RA + FM patients was higher by 15.4% than in RA patients. The incidence of high RAID disease activity (>6 points) in patients with RA and RA + FM corresponded to the high incidence by DAS28-ESR.

Table 2. RAID subscales in RA patients depending on FM comorbidity

RAID subscales РА (n=38) РА + ФМ (n=25) р
Pain Ме [Р25; Р75] 6 [6; 8] 8 [7; 9] <0,05
Pain (specific index) Ме [Р25; Р75] 1.26 [1.26; 1.68] 1.64 [1.47; 1.89] <0,05
Functional capacity Ме [Р25; Р75] 7 [6; 8] 5 [5; 6] <0,01
Functional capacity

(specific index)

Ме [Р25; Р75] 1.09 [0.96; 1.28] 0.80 [0.8; 0.96] <0,01
Fatigue Ме [Р25; Р75] 6 [5; 6] 8 [7; 8] <0,01
Fatigue (specific index) Ме [Р25; Р75] 0.9 [0.75; 0.9] 1.20 [1.05; 1.20] <0,01
Sleep Ме [Р25; Р75] 5 [5; 6] 8 [7; 9] <0,05
Sleep (specific index) Ме [Р25; Р75] 0.6 [0.6; 0.72] 0.96 [0.84; 1.08] <0,001
Physical well-being Ме [Р25; Р75] 6 [5; 7] 5 [4; 5] <0,001
Physical well-being (specific index) Ме [Р25; Р75] 0.72 [0.6;0.84] 0.60 [0.48; 0.60] <0,001
Emotional well-being Ме [Р25; Р75] 5 [4; 6] 6 [5; 6] >0.05
Emotional well-being (specific index) Ме [Р25; Р75] 0.6 [0.48; 0.72] 0.72 [0.60; 0.72] >0.05
Coping Ме [Р25; Р75] 6 [5.25; 7.75] 7 [6; 7] >0.05
Ability to work (specific index) Ме [Р25; Р75] 0.78 [0.63; 0.93] 0.77 [0.72; 0.84] >0.05
RAID (final) Ме [Р25; Р75] 5.96 [5.26; 6.91] 6.88 [6.29; 7.02] <0,05
RAID >6 n (%) 18 (47,4%) 19 (76.0%) <0.05
RAID (retest) Ме [Р25; Р75] 5.84 [5.17; 6.86] 6.91 [6.31; 7.12] <0,05
RAID-retest >6 n (%) 18 (47,4%) 19 (76.0%) <0.05

Correlation analysis (Table 3) confirmed the existence of statistically significant associations between RAID index and disease activity (NTJ, NSJ, DAS28-ESR), HAQ index, laboratory markers of inflammatory process in RA patients and RA + FM patients.

Table 3. Correlation of RAID index with disease activity in RA patients depending on comorbid FM

Indexes RAID — RA (n=38) RAID — RA+FM (n=25)
r p r p
NTJ 0.62 <0,01 0.64 <0.01
NSJ 0.78 <0.001 0.72 <0.01
ESR 0.42 <0.05 0.43 <0.05
CRP 0.41 <0.05 0.44 <0.05
DAS28-ESR 0.72 <0.005 0.67 <0.01
HAQ-DI 0.67 <0.005 0.61 <0,05

Discussion

The results obtained in the study are consistent with those of other studies that have found strong correlations between RAID and disease activity rates (DAS28-ESR, DAS28-SRB, HAQ-DI) in RA patients [1, 8, 9]. In M. Medina (2014), higher RAID indices were noted in RA patients with comorbid FM [4].

In conclusion, it should be noted that comorbid FM increases impact on the health status of patients with RA, and RAID questionnaire is a simple and sensitive tool for evaluation additional negative influence of FM on RA patients.

References

  • 1. Gossec L., Paternotte S., Aanerud G.J. et al. (2011) Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative. Ann. Rheum. Dis., 70(6): 935–942. doi: 10.1136/ard.2010.142901.
  • 2. Holten K., Sexton J., Kvien T.K. et al. (2018) Comparative analyses of responsiveness between the Rheumatoid Arthritis Impact of Disease score, other patient-reported outcomes and disease activity measures: secondary analyses from the ARCTIC study. RMD Open, 4: e000754. doi: 10.1136/rmdopen-2018–000754.
  • 3. Joharatnam N., McWilliams D.F., Wilson D. et al. (2015) A cross-sectional study of pain sensitivity, disease-activity assessment, mental health, and fibromyalgia status in rheumatoid arthritis. Arthritis Res. Ther., 17(1): 11.
  • 4. Мedina M. & Papasidero, S. & Chaparro del Moral, Rafael & Rillo, Oscar (2014) SAT0057 Fibromyalgia Tender Points in Patients with Rheumatoid Arthritis. Ann. Rheum. Dis., 72(Suppl. 3): A599–A599. 10.1136/annrheumdis-2013-eular.1783. DOI: 10.1136/annrheumdis-2013-eular.1783.
  • 5. Perebetyuk L.S., Stanislavchuck M.A. (2015) Prevalence and clinical features of fibromyalgia according to the criteria ACR1990, mACR2010, and SIQR scale in Ukrainian cohort of patients with rheumatoid arthritis. Ukr. Rheum. J., 61(3): 40–45.
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  • 7. Ranzolin A., Brenol J.C., Bredemeier M. et al. (2009) Association of concomitant fibromyalgia with worse disease activity score in 28 joints, health assessment questionnaire, and short form 36 scores in patients with rheumatoid arthritis. Arthritis. Rheum., 61(6): 794–800.
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  • 9. Stanislavchuk M.A., Zaichko K.O. (2019) Cross-cultural adaptation and validation of the Ukrainian version of RAID in patients with rheumatoid arthritis. Ukr. Rheum. J., 77(3): 51–55.
  • 10. Wolfe F., Clauw D.J., Fitzcharles M.A. et al. (2011) Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J. Rheumatol., 38(6): 1113–1122.

ВЛИЯНИЕ ФИБРОМИАЛГИИ НА СОСТОЯНИЕ ЗДОРОВЬЯ БОЛЬНЫХ РЕВМАТОИДНЫМ АРТРИТОМ СОГЛАСНО ОПРОСНИКУ RAID

С.В. Шевчук1, 2, Ю.С. Сегеда2, 1, Ю.Л. Шкаровский1, В.М. Хоменко1

1Винницкий национальный медицинский университет им. Н.И. Пирогова
2Научно-исследовательский институт реабилитации лиц с инвалидностью Винницкого национального медицинского университета им. Н.И. Пирогова

Резюме. Актуальность. У пациентов с ревматоидным артритом (РА) наряду с болью в суставах часто присутствует нейропатическая или диффузная мышечная боль, связанная с феноменом центральной сенситизации. Фибромиалгия (ФМ) существенно модифицирует течение РА, поэтому адекватный контроль аутоиммунного воспалительного процесса в синовиальных суставах не всегда обеспечивает эффективный контроль болевого синдрома. Цель исследования — оценить влияние ФМ на состоя­ние здоровья пациентов с РА согласно опроснику RAID. Материалы и методы. В исследование были включены 63 пациента с РА (87,3% женщин) в возрасте 50,0 [42; 55] лет, с умеренной и высокой активностью заболевания (DAS28 >3,2). РА диагностирован по критериям ACR/EULAR (2010). Наличие сопутствующей ФM установлено по mACR 2010. Влияние заболевания на общее состояние пациента определено с помощью RAID (вариант — украинский для Украины). Результаты. У 25 (39,7%) пациентов с РА отмечено наличие генерализированного болевого синдрома, жалобы на постоянную усталость, нарушения сна и психоэмоциональные расстройства. По критериям mACR2010 у этих пациентов диагностирована ФM. У больных РА при коморбидности с ФМ регистрировали более высокие (на 15–20%) показатели индекса RAID, которые достоверно ассоциировались с показателями активности заболевания — количеством болезненных и отечных суставов, DAS28-СОЭ, HAQ (r>0,6, p<0,01) и лабораторными маркерами активности воспалительного процесса — СОЭ, СРБ (r=0,4, p<0,05). Вывод. Коморбидность ФМ повышает влияние на состояние здоровья больных РА, а опросник RAID — это простой и чувствительный инструмент для оценки дополнительного негативного влияния ФМ состояние здоровья больных РА.

Ключевые слова: ревматоидный артрит, фибромиалгия, ревматоидный артрит, Rheumatoid Arthritis Impact of Disease (RAID).

Mailing address:
Shkarivskyi Yuri Leonidovich
E-mail: shkarovskiy2014@gmail.com

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