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Burden of rheumatoid arthritis on patients’ work productivity and quality of life

Burden of rheumatoid arthritis on patients’ work productivity and quality of life Background: To determine the burden of Rheumatoid Arthritis (RA) on patients’ work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. Methods: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. Results: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. Conclusions: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control. Keywords: Rheumatoid arthritis, Quality of life, Work performance, Surveys, Latin America Introduction population, and this prevalence varies from 0.4 to 1.6% Rheumatoid Arthritis (RA) is an autoimmune disease in Latin America population [7–9]. that causes chronic inflammation and proliferation in Since RA is not curable, the goals of RA therapy are to the synovial tissue of joints, leading to cartilage damage reach disease remission or to achieve low disease activity and joint destruction [1–3]. Irreversible damage occurs [10, 11]. Aggressive treatment in early RA has shown to early and continue throughout the patient’s life [4–6]. reduce functional disability over time, and positively in- RA affects approximately 1% of the United States (US) fluence employment [12, 13]. Lack of optimal control leads to joint damage and loss of physical function, work impairment, and finally permanent work disability. Un- * Correspondence: rxavier10@gmail.com 1 ceasing joint injury and irreversible loss of physical func- Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil tioning will negatively impact patients’ work Full list of author information is available at the end of the article performance and/or employability. A recent study © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Xavier et al. Advances in Rheumatology (2019) 59:47 Page 2 of 11 showed that work disability rates increases in accordance Item Work Limitations Questionnaire (WLQ-25), 36- to disease duration: 35, 39, and 44% after 5, 10, and 15 Item Short Form Health Survey (SF-36) and EuroQol 5 years of RA diagnosis, respectively [14]. Dimensions Questionnaire 3 level version (EQ-5D-3 L). There is still a need of detailed information on how All standardized questionnaires were adequately trans- RA patients are successful on preserving employability lated into Brazilian Portuguese and Spanish. Some of the and how is the current burden of RA on work product- instruments had already been validated with final ver- ivity in Latin America. sions reported in previous publications or by their copy- Therefore, this study primarily aimed to determine the right holders. [16–20] The remaining questionnaires and burden of RA on patients’ work productivity and health versions were validated within the scope of the study, related quality of life (HRQoL) and to explore the im- using usual methods in the field. pact of related variables. Additionally, the progression of RA and its impact on work productivity and HRQoL Work productivity were also investigated. WALS is a 12-item questionnaire that assesses patient’s limitation at work without a recall period. Answers op- Methods tions consist of a 4-point Likert scale that ranges from 0 Study design and eligibility criteria (no difficulties) to 3 (not able to do). Dimensions in- PROSE RA study (Patient Reported Outcomes Survey of cludes difficulty getting to and from work, lifting, work- Employment among patients with RA) is an inter- ing with hands, crouching/bending/kneeling/reaching, national multicenter prospective survey. Patients were work pace, concentration, standing/sitting for long pe- included from May/2012 to September/2015 in 18 riods, and meeting work demands. Overall score ranges rheumatology public and private clinics from four Latin from 0 to 36 points and higher measures indicate greater American countries: Argentina, Brazil, Colombia and limitation [21]. Mexico. All sites in Argentina, Colombia and Mexico WPAI:RA contains six questions to measure disabil- were private, while 2 out of 3 Brazilian sites were pub- ities in paid and unpaid work in the last seven days. Re- licly funded. Patients diagnosed with RA identified in sults include four scores that summarize the percentage outpatient routine visits were invited to participate and of: work time missed due to health; impairment while were included if they met the eligibility criteria: Age be- working due to health; activity impairment due to tween 21 and 55 years (representing a working age health; and Overall work impairment score due to health group); documented diagnosis of RA as defined by the problems. The scores ranges from 0 to 100 points and revised 1987 classification criteria of the American Col- higher measures indicate greater limitation in each do- lege of Rheumatology (ACR) [15]; and willing to provide main [22]. informed consent to participate in the study. Patients WLQ-25 is composed by 25-items and focuses on not able to give informed consent and/or to complete presenteeism and the proportion of work-time with limi- the study procedures were excluded. Two different ana- tation as opposed to the degree of difficulty or severity lyses were performed: cross-sectional to determine the of limitations. It assesses four dimensions of presentee- burden of RA on patients’ work productivity and ism while at work: physical demands, time management, HRQoL (primary) considering the baseline answers to mental-interpersonal demands and output demands. selected patient-reported outcomes (PROs), and longitu- Questions regarding work productivity and performance dinal over 1 year to evaluate the progression of RA and over the past 2–4 weeks were answered using a 5-point its impact on work productivity and HRQoL Likert scale, ranging from 0 (none of the time) to 4 (all (secondary). of the time). Each scale was scored separately and scores were converted from 0 to 100, where higher scores rep- Data collection resent increased limitations [23, 24]. Five study visits were performed every three months over 1-year follow-up. During each visit, participants an- Health-related quality of life swered an interview that assessed data about sociodemo- SF-36 is a composed by 36 questions grouped into 8 do- graphic and clinical characteristics, lifestyle behavior, mains (physical functioning, role-physical, bodily pain, disease activity, use of Disease-Modifying Antirheumatic general health, vitality, social functioning, role- Drugs (DMARDs), direct medical resource utilization emotional, and mental-health). Two summary measures and medication coverage/insurance. Impact on work are also provided: Physical Component Summary (PCS) productivity and HRQoL was evaluated using standard- and Mental Component Summary (MCS). The raw score ized instruments: Workplace Activity Limitation Scale of each dimension was converted into a value from 0 (WALS), Work Productivity and Activity Impairment (worst possible health state) to 100 (best possible health Questionnaire - Rheumatoid Arthritis (WPAI:RA), 25- state). All scales were standardized to the 1998 general Xavier et al. Advances in Rheumatology (2019) 59:47 Page 3 of 11 US population using the norm base scale algorithm. normal distribution using the Shapiro-Wilk and Scale score < 45 can be interpreted as being below the Kolmogorov-Smirnov tests. To compare means, vari- average range for the general population [25]. ables with normal distribution were analyzed by the Stu- EQ-5D-3 L assesses health status through 5 domains dent’s t-test and those with non-normal distribution by (mobility, self-care, usual activities, pain/discomfort and Mann-Whitney or Wilcoxon nonparametric tests. Linear anxiety/depression) considering 3 levels: no problems, regression was used to build a multivariate model to as- some problems, extreme problems. Additionally, a Vis- sess the association between outcomes and exposure ual Analogue Scale (EQ-VAS) records respondents’ self- variables, controlled for possible confounders and inter- rated health from “Best imaginable health state”=0 to actions. Due to the small sample size for each country, “Worst imaginable health state”=100. Utility score repre- bivariate and multivariate analyses were performed con- sents a scale between death = 0 and perfect health = 1 sidering the entire sample only. Analysis of the impact and is derived from the answers to each dimension, cal- of disease progression (longitudinal) on work productiv- culated using the United Kingdom algorithm [26, 27]. ity and HRQoL was assessed through the difference on mean scores between study visits 1 and 5. Thus, these Disease progression differences are shown and tested among disease progres- Multi-Dimensional Health Assessment Questionnaire sion groups: “Improvement or maintenance” and (MDHAQ) was used in the first and last visits to evalu- “Worsening”. ate disease activity, which is a 4-domains measure: phys- Only valid answers were used for all PROs. Guidelines ical function (FN), pain (PN), Rheumatoid Arthritis [21, 23, 25, 26, 28] from each standardized instruments Disease Activity Index (RADAI) and patient global esti- report different strategies to deal with missing data as mate (PTGL). Final disease activity measure was ob- follows: MDHAQ (if at least one question left un- tained using Rheumatology Assessment Patient Index answered in any domain, patient excluded from this spe- Data 3 measures (RAPID3), calculated from the answers cific analysis); WALS (patient excluded from specific of three MDHAQ domains (FN, PN and PTGL). analysis, if more than two questions left unanswered; RAPID3 score ranges from 0 to 30 points and classify values estimated through the mean of answered data, if patients into four groups: remission (≤3 points), low se- until two questions left unanswered or the answer of any verity (3.1 to 6 points), moderate severity (6.1 to 12 question “refused”); WPAI:RA (questionnaires with points) and high severity (> 12 points) [28]. Disease pro- missing answers did not have the corresponding score gression was defined as disease activity modification dur- calculated); WLQ (patient excluded from specific ana- ing the study period, considering the interval between lysis if > 2 questions were left unanswered); SF-36 (miss- the first and last visits, classified in the following cat- ing values estimated through the mean of answered data egories: Improvement or maintenance; and Worsen. in the same scale for patients with responses for at least half of the domain questions); and EQ-5D-3 L (patient Sample size calculation excluded of specific analysis, if any question left PROSE RA study was primarily designed to assess how unanswered). RA impacts on work productivity and HRQoL at base- Stata (version MP12) and R Project (version 3.2) were line and also to analyze association with exposure vari- adopted to perform the analysis with a 95% confidence ables. Thus, sample size was calculated based on interval and p-value≤0.05. assumptions of potential differences between these groups from published data [20, 29–32]. Simulations for Ethical approval a descriptive approach were performed to assure an ad- Research was reviewed and approved by Independent equate precision of estimated parameter using two dif- Ethics Committee according to study site and respon- ferent margins of error: a score difference observed by sible committees are listed in Additional file 1: Table S1. each subgroup and a fixed value of 5.0% of the max- All procedures were in accordance with the ethical stan- imum in each scale. Considering ɑ = 0.05 and a power of dards from each country and with the Helsinki declar- 0.80 and adopting a conservative approach, the higher ation and its later amendments or comparable ethical estimated sample size was select (N = 280) assuring that standards. Written informed consent and authorization the study would have power to detect the smallest to use and/or disclose his/her anonymised health data difference. was obtained from all participants. Statistical analysis Results Descriptive analysis was performed through means and Sociodemographic and clinical characteristics standard deviation to quantitative variables, and fre- The study enrolled 290 patients at baseline: 75 (25.9%) quency to qualitative variables. Data were tested for from Argentina, 75 (25.9%) from Mexico, 72 (24.8%) Xavier et al. Advances in Rheumatology (2019) 59:47 Page 4 of 11 from Colombia and 68 (23.4%) from Brazil. Sociodemo- 95%CI = 12.10 to 19.72; p < 0.001). The “absenteeism and graphic and clinical characteristics are shown in Tables 1 presenteeism” category was decreased by: medication and 2. coverage/insurance (β = − 2.70; 95%CI = -4.95 to − 0.45; NA = Not applicable. p = 0.021) and consultations in the last 3 months (β = − RA = Rheumatoid Arthritis. 1.26; 95%CI = -2.40 to − 0.11; p = 0.033). Having per- SD = Standard Deviation. formed ancillary tests in the last 3 months (β = 1.27; DMARDs = Disease-Modifying Antirheumatic Drugs. 95%CI = 0.19 to 2.53; p = 0.023) and previous orthopedic RA = Rheumatoid Arthritis. surgery (β = 1.80; 95%CI = 0.32 to 3.22; p = 0.019) in- RAPID3 = Rheumatology Assessment Patient Index creased “absenteeism and presenteeism”. Impairment in Data 3 measures. regular daily activities was decreased by overweight/ SD = Standard Deviation. obesity (β = − 7.14; 95%CI = -14.03 to − 0.25; p = 0.042); and increased by disease activity (β = 19.47; 95%CI = Work productivity at baseline 16.67 to 22.28; p < 0.001) and female group (β = 12.14; Table 3 shows descriptive analysis of WALS, WPAI:RA 95%CI = 1.08 to 23.21; p = 0.032). and WLQ-25. Results stratified in accordance with ex- For the total sample, WLQ-25 physical demands scale posure variables for total sample and final models for (40.3%) was the most affected due to RA, ranging from each questionnaires’ measures are shown in Additional 44.0% in Mexico to 35.5% in Colombia. Productivity loss file 1: Tables S2 and S3, respectively. represented by WLQ-25 index was 7.0% (SD = 5.1), ran- RA = Rheumatoid Arthritis. ging from 7.8% (SD = 5.6) in Colombia to 5.9% (SD = SD = Standard Deviation. 4.5) in Brazil. In multivariate final model, higher educa- WALS=Workplace Activity Limitation Scale. tional levels - technical or trade school to complete post- WLQ-25 = 25-item Work Limitations Questionnaire. graduate education - (β = − 0.36; 95%CI = -0.70 to − 0.02; WPAI:RA = Work Productivity and Activity Impair- p = 0.039) and having undergone a previous orthopedic ment Questionnaire - Rheumatoid Arthritis. surgery (β = − 0.50; 95%CI = -1.00 to − 0.01; p = 0.045) Overall mean WALS score in total sample was 9.0 decreased productivity losses. (SD = 6.1), ranging from 8.2 (SD = 6.3) in Mexico to 10.6 (SD = 6.8) in Brazil. At least 40.3% of RA patients re- Health-related quality of life ported some disability in each of the WALS questions. Table 4 shows descriptive analysis of HRQoL measures. Main limitations informed in the workplace were diffi- These measures were stratified in accordance with ex- culty to crouch, bend, kneel or work in awkward posi- posure variables for total sample and final model for tions (84.0%) and to lift, carry or move objects (80.1%). each of the questionnaires’ measures are shown in Add- A similar pattern was observed among participating itional file 1: Tables S4 and S5. countries. Multivariate analysis showed that higher work EQ-5D-3 L = EuroQol 5 Dimensions Questionnaire 3 limitation according to WALS was observed when pa- level version. tients had medication coverage/insurance (β = 2.35; MCS = Mental Component Score. 95%CI = 0.21 to 4.50; p = 0.031) and increased disease PCS=Physical Component Score. activity level (β = 3.67; 95%CI = 3.01 to 4.34; p < 0.001). RA = Rheumatoid Arthritis. Employment was reported by 60.3% of the total re- SD = Standard Deviation. spondents of WPAI:RA - 72.6% in Argentina, 62.5% in SF-36 = 36-Item Short Form Health Survey. Colombia, 57.3% in Mexico and 44.2% in Brazil (data Considering data for general population, seven of not shown). Considering total sample, the ability to per- eight scales from SF-36 questionnaire in total sample form usual activities due to RA was the mostly affected have shown scores slightly below the reference value category (42.5%; SD = 30.9), and presenteeism was the (lower limit: 45). Value observed in the scale “Vitality” most impaired productivity dimension (29.5%; SD = for total sample was the only within the range of 45 28.8). All participating countries had a comparable pat- and 55. The same pattern was observed in each of tern. In WPAI:RA final multivariate model, having previ- the countries, with the exception of Mexico, that has ous orthopedic surgery (β = − 1.80; 95%CI = -3.28 to − shown scores within the range for the scales “Vitality” 0.31; p = 0.020), medication coverage/insurance (β = − (49.8; SD = 10.3) and “Mental Health” (46.7; SD = 2.69; 95%CI = -4.99 to − 0.39; p = 0.024) and consulta- 11.6). All PCS measures were below the reference tions in the last 3 months (β = − 1.22; 95%CI = -2.39 to − value for total sample and also for each country. 0.05; p = 0.042) decreased absenteeism; while reporting Mean estimated for MCS was above reference value having performed ancillary tests increased (β = 1.27; for total sample, and also in Brazil and Mexico. In 95%CI = 0.19 to 2.53; p = 0.023). Each disease activity themultivariateanalysis, patients whohad performed level significantly increased presenteeism (β = 15.91; ancillary tests in the last 3 months had a decrease in Xavier et al. Advances in Rheumatology (2019) 59:47 Page 5 of 11 Table 1 Description of studied sociodemographic characteristics among RA patients at baseline Characteristic Argentina Brazil Colombia Mexico Total (N = 75) (N = 68) (N = 72) (N = 75) (N = 290) N% N% N% N% N% Age [Mean/SD] 43.4 7.8 45.9 6.8 49.3 8.9 41.6 9.5 43.7 8.4 Gender Female 68 90.7 59 86.8 64 88.9 70 93.3 261 90.0 Race Mestizo NA NA 15 22.1 45 62.5 72 96 132 45.6 Caucasian/White 37 49.3 36 52.9 3 4.2 NA NA 76 26.2 Hispanic/Latin 37 49.3 NA NA 21 29.2 NA NA 58 20.0 African American NA NA 14 20.6 1 1.4 –– 15 5.2 Brazilian Indian NA NA 1 1.5 NA NA NA NA 1 0.3 Native American NA NA NA NA 1 1.4 NA NA 1 0.3 Other NA NA 2 2.9 NA NA NA NA 2 0.7 Marital Status Married 41 54.7 35 51.5 30 41.7 41 54.7 147 50.7 Single/Not ever married 20 26.7 19 27.9 24 33.3 18 24.0 81 27.9 Partner/Common law 8 10.7 4 5.9 11 15.3 5 6.7 28 9.7 Divorced 2 2.6 5 7.4 1 1.3 7 9.3 15 5.2 Separated 4 5.3 –– 3 4.2 1 1.3 8 2.8 Widowed –– 3 4.3 3 4.2 2 2.7 8 2.7 Educational level Incomplete High School 18 24.0 32 47.1 15 20.8 6 8.0 71 24.5 Complete High School 17 22.7 18 26.5 12 16.7 17 22.7 64 22.1 Technical or trade school NA NA 5 7.4 16 22.2 20 26.7 41 14.1 Complete or incomplete graduate degree 35 46.7 4 5.8 20 27.8 18 24.0 77 26.6 Complete postgraduate 2 2.6 4 5.8 9 12.5 4 5.3 19 6.6 Primary occupation Professional or technical 16 21.3 4 5.9 18 25.0 13 17.3 51 17.6 Office worker 13 17.3 3 4.4 13 18.1 4 5.3 33 11.4 Service worker 9 12.0 10 14.7 11 15.3 7 9.3 37 12.8 Sales 7 9.3 2 2.9 6 8.3 6 8.0 21 7.2 Manager, official or proprietor 4 5.3 1 1.5 6 8.3 5 6.7 16 5.5 Craftsman or foreman 2 2,7 2 2.9 2 2.8 1 1.3 7 2.4 Operative 1 1.3 3 4.4 3 4.2 1 1.3 8 2.8 Other 12 16.0 6 8.8 11 15.3 34 45.3 69 21.7 NI 11 14.7 37 54.4 2 2.8 4 5.3 54 18.6 Smoking habit Nonsmokers 40 53.3 39 57.4 47 65.3 51 68.0 177 61.0 Former smokers 22 29.3 17 25.0 20 27.8 12 16.0 71 24.5 Current smokers 13 17.4 12 17.6 5 6.9 11 14.7 41 14.2 the PCS score (β = − 2.33; 95%CI = -4.17 to − 0.49; p = 6.21; p < 0.001) and MCS, in at least 3.34 points (β = 0.013); and each category of disease activity, from re- − 3.34; 95%CI = -4.72 to − 1.96; p < 0.001). mission to high severity, decreased the score of PCS, EQ-VAS mean score ranged from 64.4 (SD = 21.5) in in at least 7.06 points (β = − 7.06; 95%CI = -7.87 to − Brazil to 75.4 (SD = 21.6) in Mexico and for the whole Xavier et al. Advances in Rheumatology (2019) 59:47 Page 6 of 11 Table 2 Description of studied clinical characteristics among RA patients at baseline Characteristic Argentina Brazil Colombia Mexico Total (N = 75) (N = 68) (N = 72) (N = 75) (N = 290) N % N% N% N% N% Clinical characteristics Body Mass Index [Mean/SD] 26.8 4.9 29.2 6.1 24.8 3.7 27.6 5.2 27.0 5.3 Comorbidities 53 70.7 59 86.8 40 55.6 40 53.3 192 66.2 Patients who underwent at least one previous orthopedic surgery 18 24.0 12 17.6 11 15.3 7 9.3 48 16.6 Disease characteristics Disease duration (years) [Mean/SD] 8.9 9.0 10.8 6.7 8.6 7.3 7.7 7.2 9.0 7.7 Time since symptoms onset (years) [Mean/SD] 9.7 9.0 12 7.8 9.5 7.3 9.4 7.4 10.1 8.0 Patients with medication coverage/insurance 68 90.7 47 69.1 69 95.8 55 73.3 239 82.4 Use of DMARDs 66 88.0 60 88.2 62 86.1 69 92.0 260 89.7 Disease activity (RAPID3 score) Remission 9 12.0 3 4.4 6 8.3 15 20.0 33 11.4 Low severity 17 22.7 1 1.5 9 12.5 11 14.7 38 13.1 Moderate severity 14 18.7 23 33.8 21 29.2 21 28.0 79 27.2 High severity 22 29.3 38 55.9 31 43.1 22 29.3 113 39.0 Direct medical resource utilization in the last three months Patients with at least one outpatient visit 58 77.3 52 76.5 58 80.5 56 74.7 224 77.2 Patients with at least one visit to perform tests 47 62.7 48 70.6 45 62.5 49 65.3 196 67.9 Patients who underwent at least one surgery (any type) 4 5.3 1 1.5 4 5.6 1 1.3 10 3.4 sample was 69.8 (SD = 20.4). Mean utility score was 0.67 observed between these measures (p =0.270). How- (SD = 0.23) for total sample and ranged from 0.62 (SD = ever, the majority of patients (79.4%) has improved or 0.19) to 0.71 (SD = 0.23) among countries. Final multi- maintained the disease activity level during the 1-year variate model for EQ-VAS has shown that patients with follow-up period. a longer disease duration (≥9 years) (β = − 5.19; 95%CI = Considering differences between the first and last -9.52 to − 0.85; p = 0.019) and presenting worsening of study visits, worsening in the disease activity showed an disease activity level (β = − 10.74; 95%CI = -12.81 to − association with an increase on impact on work product- 8.68; p < 0.001) have a decrease in the score. Beside this, ivity and HRQoL. Patients who had improvement/main- use of DMARDs increased EQ-VAS score (β = 8.39; tenance had also an improvement in the assessed 95%CI = 1.52 to 15.25; p = 0.020). measures and those who worsened also had a worsening Regarding utility scores from EQ-5D-3 L instrument, in the scores, except for WLQ-25. However, a statisti- ancillary test multivariate analysis indicates that over- cally significant difference was observed only for WALS weight/obese patients (β = − 0.06; 95%CI = -0.11 to − (p = 0.001); WPAI:RA domains “presenteeism” (p = 0.003; p = 0.039) and those with a longer disease 0.020) and “impairment of regular daily activities” (p = duration (≥9 years) (β = − 0.05; 95%CI = -0.10 to − 0.01; 0.017); components of SF-36: physical (p < 0.001) and p = 0.012) have a decrease in the utility score. Utility mental (p < 0.001); and EQ-5D-3 L utility score (p = score is also reduced with the increase of the disease ac- 0.007) - Table 5. tivity level (β = − 0.12; 95%CI = -0.14 to − 0.10; p < EQ-5D-3 L = EuroQol 5 Dimensions Questionnaire 3 0.001). On the other hand, mestizos patients showed an level version. increasing in utility scores (β = 0.06; 95%CI = 0.01 to HRQoL = Health-Related Quality of Life. 0.11; p = 0.010). WALS=Workplace Activity Limitation Scale. WLQ-25 = 25-item Work Limitations Questionnaire. Disease progression and impact on work productivity and WPAI:RA = Work Productivity and Activity Impair- HRQoL ment Questionnaire - Rheumatoid Arthritis. It was observed a slightly higher mean of RAPID3 SD = Standard Deviation. score in Visit 1 (10.7; SD = 6.6) than in Visit 5 (9.7; SF-36 = 36-Item Short Form Health Survey. SD = 6.7), but no statistical significant difference was VAS=Visual Analogue Scale. Xavier et al. Advances in Rheumatology (2019) 59:47 Page 7 of 11 Table 3 Work productivity assessed through WALS, WPAI:RA and WLQ-25 questionnaires among RA patients at baseline Work Productivity Argentina Brazil Colombia Mexico Total Mean SD Mean SD Mean SD Mean SD Mean SD WALS N =52 N =22 N =64 N =68 N = 206 1.Get to and from work and maintain punctuality [N/%] 18 34.6 11 50.0 30 46.9 24 35.3 83 40.3 2. Getting to the workplace [N/%] 26 50.0 11 50.0 43 67.2 36 52.9 116 56.3 3. Sitting for long periods of time at your job [N/%] 17 32.7 10 45.5 38 59.4 34 50.0 99 48.1 4. Standing for long periods of time at your job [N/%] 34 65.4 15 68.2 49 76.6 46 67.6 144 69.9 5. Lift, carry or move objects [N/%] 39 75.0 18 81.8 52 81.3 56 82.4 165 80.1 6. Working with your hands [N/%] 35 67.3 17 77.3 45 70.3 30 44.1 127 61.7 7. Crouching, bend, kneel or work in awkward positions [N/%] 43 82.7 20 90.9 52 81.3 58 85.3 173 84.0 8. Stretch out [N/%] 33 63.5 19 86.4 40 62.5 37 54.4 129 62.6 9. With the schedule of hours of work that your job requires [N/%] 18 34.6 12 54.5 30 46.9 30 44.1 90 43.7 10. With the pace of work that your job requires [N/%] 27 51.9 12 54.5 37 57.8 42 61.8 106 51.5 11. Meet your current job demands [N/%] 25 48.1 14 63.6 36 56.3 37 54.4 110 53.4 12. To concentrate and keep your mind on your work [N/%] 19 36.5 12 54.5 7 10.9 25 36.8 92 44.7 Overall score of WALS (0–36) 8.4 5.6 10.6 6.8 9.7 6.0 8.2 6.3 9.0 6.1 WPAI:RA N =73 N =52 N = 72 N =75 N = 272 Normal Daily Activities % Daily activity impairment due to RA 34.0 28.2 56.1 27.4 46.7 29.0 36.5 33.8 42.5 30.9 Professional Activities % Impairment while working due to RA (presenteeism)* 23.9 23.9 32.6 26.8 40.5 32.2 23.1 28.5 29.5 28.8 % Work time missed due to RA (absenteeism)* 12.0 27.5 5.8 23.5 7.5 21.6 8.4 18.8 9.0 23.2 % Overall work impairment due to RA (absenteeism and presenteeism)* 10.3 25.0 5.9 23.9 7.6 21.9 8.9 20.3 8.6 22.6 WLQ-25 N =59 N =36 N =43 N =53 N = 191 % work impairment due to physical demands 41.1 24.7 37.7 24.1 35.5 24.0 44.0 28.7 40.3 21.4 % work impairment due to time demands 33.5 24.7 29.3 30.6 32.4 26.8 27.9 29.0 30.9 28.0 % work impairment due to output demands 27.6 24.4 18.1 19.3 29.9 25.8 22.7 23.3 24.9 23.8 % work impairment due to mental-interpersonal demands 20.1 21.9 15.2 18.0 20.9 24.8 16.1 20.1 18.2 23.8 WLQ-25 index (%) 7.5 5.1 5.9 4.5 7.8 5.6 6.5 4.9 7.0 5.1 Discussion presenteeism, indicating that patients are working with Our sample was comprised of patients from 4 Latin reduced performance and which seems to lead to un- American countries, mostly middle-aged, female, from employment [33–36]. For example, WPAI presenteeism multiethnic origin, married with a technical or profes- measure (percentage of impairment while working due sional occupation. The educational level was well- to RA) in our sample was 28.8%, while healthy controls distributed in the total sample, but Brazilian patients in a previous study in Sweden reported a mean impair- had a higher frequency of incomplete or complete high ment of 20.9%. [37] Regarding HRQoL, physical aspect school only. This observation may be at least partially of the disease seems to be the major impairing condition explained by the type of funding for study sites in the [38–41]. Although these available data, there are several sample, once only Brazil had publicly-funded healthcare standard PROs that assess these outcomes from different services enrolling patients and those facilities usually at- perspectives, and this study analyzed a unique RA popu- tend people with lower income and lower educational lation using these different instruments. level in the country. Our results about burden of RA on work productivity The burden of RA on Latin-American patients’ work assessed at baseline demonstrated an important impact productivity and HRQoL was comprehensively assessed of the disease on patients’ life, related to several dimen- using standard PROs. Thus, it was possible to descrip- sions according to the instrument, and corroborate tively compare these data with findings from other con- international data that patients are working with reduced texts and countries. In summary, RA was related with performance. The overall work impairment due to RA at Xavier et al. Advances in Rheumatology (2019) 59:47 Page 8 of 11 Table 4 Health-related quality of life assessed through SF-36 and EQ-5D-3 L questionnaires among RA patients at baseline Health-related Quality of Life Argentina Brazil Colombia Mexico Total Mean SD Mean SD Mean SD Mean SD Mean SD SF-36 N = 75 N = 68 N = 72 N = 75 N = 290 Vitality 46.9 10.9 47.0 9.5 47.9 10.2 49.8 10.3 47.9 10.3 Mental health 42.5 11.4 44.3 12.3 43.7 10.4 46.7 11.6 44.3 11.5 Social functioning 41.9 11.6 40.1 11.3 40.6 11.5 44.2 10.9 41.8 11.4 Bodily pain 43.2 10.7 36.6 8.3 39.3 10.1 43.5 10.7 40.8 10.4 Role physical 42.4 11.5 37.0 11.5 39.1 10.7 43.0 9.7 40.5 11.1 General health 41.9 9.7 38.5 11.9 39.5 8.9 41.6 12.2 40.4 10.8 Role emotional 39.9 13.9 41.2 13.5 37.5 11.6 42.1 11.3 40.2 12.7 Physical functioning 38.5 11.0 32.0 8.6 37.6 10.6 40.2 12.2 37.2 11.1 Mental Component Score (MCS) 43.4 11.9 47.3 11.9 43.9 9.9 47.2 11.3 45.4 11.3 Physical Component Score (PCS) 41.8 9.8 33.6 9.6 38.7 9.1 41.5 10.7 39.1 10.3 EQ-5D-3 L N=73 N=68 N =70 N =75 N = 286 Overall Value (0–100) 71.5 16.6 64.4 21.5 67.4 20.2 75.4 21.6 69.8 20.4 Utility Score (0–1) 0.67 0.25 0.62 0.19 0.66 0.25 0.71 0.23 0.67 0.23 baseline in our sample was similar or lower than the ob- When HRQoL was assessed at baseline, a major im- served in previous studies, depending on the characteris- pact on physical aspects was observed, with lower phys- tics of studied sample [33–35]. The work limitations ical SF-36 score (when compared with mental score), as related to presenteeism were also investigated using described in the literature. EQ-VAS value estimated in WALS measures and our patients are classified as our study was 69.8 (SD = 20.4), which is similar to those having high severity of work place disability [36]. In reported for Brazilian RA patients (mean score: 63 to the present study, all WLQ-25 subscales at baseline 74) [43], and different from Mexican patients (mean were higher than results observed in US populations score: 49.5) with osteoarthritis, RA or chronic low-back of RA patients. A remarkable difference is noted in pain [44]. Utility measure calculated was 0.67 and no physical demands scale, indicating that Latin Ameri- studies describing utility among Latin American RA pa- can patients are more limited in work environment tients were found to date. This measure is usually used mainly in this scale [38, 42]. to define public health policies, resource allocation and Table 5 Comparison between differences in work productivity and HRQoL scores and disease progression from the first to the last study visit Outcomes Disease Progression Improvement or maintenance Worsening p-value Mean Difference SD Mean Difference SD Work Productivity WALS −0.9 4.1 1.9 4.2 0.001 WPAI:RA Absenteeism −0.7 25.3 5.0 14.7 0.118 Presenteeism −3.7 24.9 11.0 21.2 0.020 Absenteeism and Presenteeism −0.9 26.7 5.0 14.8 0.101 Impairment of regular daily activities −5.5 28.4 7.0 27.0 0.017 WLQ-25 0.4 7.3 −0.2 8.1 0.723 HRQoL SF-36 PCS 2.9 7.1 −1.7 7.1 < 0.001 MCS 1.1 10.3 −4.0 6.6 < 0.001 EQ-5D-3 L Overall VAS Value 5.2 22.8 −1.4 17.7 0.142 Utility score 0.03 0.25 −0.06 0.18 0.007 Xavier et al. Advances in Rheumatology (2019) 59:47 Page 9 of 11 evaluation of services and programs, as it works as a observation suggests that this is a particularly refractory proxy of how people value changes in health status [45], population or that the management could be subopti- highlighting the need for these studies in Latin America. mal. Further analyses of the data, including medication It is known that multiple factors act to generate work use, will be done to address this issue. impairment and poor HRQoL [46]. Obesity, living with- The aforementioned associations of HRQoL and work out partner, being mestizo, the presence of comorbidi- productivity among different stratum of study popula- ties, having medication insurance/coverage, longer tion were not yet well established and, thus, more stud- disease duration, having performed ancillary test and ies are needed in order to infer a causal relationship [14, consultations and a previous orthopedic surgery were as- 40, 46, 48–53]. However, it is important that healthcare sociated with a worsening in work productivity and/or professionals stay alert to those characteristics during HRQoL. An improvement in the assessed PROs scores RA patients’ management and also patients, families and was associated with a higher educational level, having the society, with the aim to minimize its effects on pa- medication insurance/coverage, being mestizo, having tients’ professional and personal lives. It is worth men- recently performed ancillary test and consultations, a tioning that health systems should be investing in history of previous orthopedic surgery and use of strategies and technologies targeting disease activity con- DMARDs. Some variables behaved as protective or risk trol among RA patients, once this seems to be a variable factors, depending on the instrument assessed, suggest- strongly related to higher burden not only to patients, ing that these relationships still needs to be further ad- but also the society. The data presented here will cer- dressed. Also, unexpectedly, obesity and overweight tainly be useful to better estimate the cost-effectiveness were associated with reduced impairment in regular of these treatment strategies, invaluable information for daily activities in the WPAI analysis, as compared to optimizing the use limited health resources in relatively underweight/normal BMI values. This finding seems in low-income countries, particularly nowadays with the conflict with our observation that obese/overweight indi- growing number of costly anti-rheumatic drugs viduals have worse quality of life (EQ-5D-3 L utility available. score) and could not be explained by our data. A similar This was the first study conducted in countries from pattern was observed for the association between greater Latin America with the aim to assess RA patients work work limitations according to WALS and medication productivity and HRQoL. This study adds knowledge in coverage/insurance. Potential confounders not collected an area scarcely studied and improves global disease in our study may play in this association. comprehension about burden of RA in Latin America. With exception of WLQ-25, all PROs were associated with disease activity. The hypothesis that the disease ac- tivity may have a great impact in these aspects of pa- Conclusion tients’ life arises from the presence of joint damage and This study highlights the importance of regular and loss of physical function in RA, which seems to be a timely disease management for RA patients, specially fo- prognostic factor in the ability to keep or get a new job cusing on the need to decrease disease activity to pro- [14, 47]. This relationship was also observed in the mote better results in PROs. An increase in disease longitudinal analysis, and confirms the finding from activity was responsible for a significant decrease in cross-sectional analysis showing that disease worsening HRQoL, and a significant increase in workplace disabil- is associated with an increase of the impact on work ities, leading to a more difficult time in maintaining or productivity and a decrease of HRQoL scores. Although seeking job opportunities. Also, multiple factors were no studies in the literature have assessed this relation- identified that seem to be associated with work impair- ship over time, this finding corroborates the main goals ment and HRQoL, but as for the protective factors, fur- proposed by EULAR (The European League Against ther research is still needed. This study’s results Rheumatism) and ACR (American College of Rheuma- highlight the need for a more comprehensive and holis- tology) – o since the disease is not entirely curable, RA tic approach to RA management and that all relevant therapy must aim to reach disease remission, and if it is stakeholders (from families to HR managers) should be not possible, to achieve low disease activity reflecting on aware of RA’s burden in patients’ everyday life. Also, it patients’ professional and personal lives [10, 11]. About sheds some light in a subject that is often overlooked, this aspect, it is important to notice that in the studied adding to the evidence that the burden of RA in QoL is population, most patients had moderate or high disease significant. Finally, the knowledge of the burden of dis- activity at baseline and maintained it during the 1-year ease in Latin America is often limited, and this study follow-up. Considering the recommendations for strat- contributes to the ever-increasing need to raise aware- egies of close monitoring and prompt therapy adjust- ness so that resource allocation is focused on tackling ments to achieve low disease activity or remission, this this issue. Xavier et al. Advances in Rheumatology (2019) 59:47 Page 10 of 11 Supplementary information Competing interests Supplementary information accompanies this paper at https://doi.org/10. The authors declare that they have no competing interests. 1186/s42358-019-0090-8. Author details Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Additional file 1: Table S1. Independent Ethics Committee/Institutional Alegre, Porto Alegre, Brazil. Centro Paulista de Investigações Clínicas (CEPIC), Review Board approvals. Table S2. Work productivity assessed through São Paulo, Brazil. Universidade Federal de São Paulo, São Paulo, Brazil. WALS, WPAI:RA and WLQ-25 questionnaires among several exposure 4 5 Morales Vargas Centro de Investigación, Guanajuato, Mexico. Fundación groups of RA patients at baseline. Table S3. Final model for the associ- Instituto de Reumatología Fernando Chalem, Bogotá, Colombia. Centro ation between work productivity (WALS, WPAI:RA and WLQ-25 scores) Integral de Reumatología – Reumalab, Medellín, Colombia. Centro de and exposure groups at baseline. Table S4. Health-related quality of life Investigaciones en Enfermedades Reumáticas (CIER), Buenos Aires, Argentina. assessed through SF-36 and EQ-5D-3L questionnaires among several ex- 8 9 Desarrollos Biomédicos y Biotecnológicos, Monterrey, Mexico. Circaribe, posure groups of RA patients at baseline. Table S5. Final model for the Barranquilla, Colombia. CEIM Investigaciones Medicas, Buenos Aires, association between health-related quality of life (SF-36 and EQ-5D-3L Argentina. Instituto Médico Especializado (IME), Buenos Aires, Argentina. scores) and exposure groups at baseline. 12 13 AbbVie Farmacêutica Ltda, São Paulo, Brazil. Unidad de Investigación en Enf. Crónico-Degenerativas, Guadalajara, Mexico. Abbreviations Received: 1 November 2018 Accepted: 21 October 2019 ACR: American College of Rheumatology; DMARDs: Disease-Modifying Antirheumatic Drugs; EQ-5D-3 L: EuroQol 5 Dimensions Questionnaire 3 level version; EQ-VAS: EQ Visual Analogue Scale; FN: Physical function; HRQoL: Health related quality of life; MCS: Mental Component Summary; References MDHAQ: Multi-Dimensional Health Assessment Questionnaire; PCS: Physical 1. Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Component Summary; PN: Pain; PROs: Patient-reported outcomes; PROSE RA Drug Discov. 2003;2:473–88. study: Patient Reported Outcomes Survey of Employment among patients 2. Choy EH, Panayi GS. Cytokine pathways and joint inflammation in with RA; PTGL: Patient's global assessment; RA : Rheumatoid Arthritis; rheumatoid arthritis. N Engl J Med. 2001;344:907–16. RADAI: Rheumatoid Arthritis Disease Activity Index; RAPID3: Rheumatology 3. Drosos AA. Newer immunosuppressive drugs: their potential role in Assessment Patient Index Data 3 measures; SD: Standard Deviation; SF- rheumatoid arthritis therapy. Drugs. 2002;62:891–907. 36: 36-Item Short Form Health Survey; WALS: Workplace Activity Limitation 4. Goldring SR. Pathogenesis of bone and cartilage destruction in rheumatoid Scale; WLQ-25: 25-Item Work Limitations Questionnaire; WPAI:RA: Work arthritis. Rheumatology (Oxford) 2003;42 Suppl 2:ii11–6. Productivity and Activity Impairment Questionnaire – Rheumatoid Arthritis 5. Lee SJ-A, Kavanaugh A. Pharmacological treatment of established rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2003;17:811–29. Acknowledgments 6. Lindqvist E. 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Springer Journals
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Copyright © 2019 by The Author(s)
Subject
Medicine & Public Health; Rheumatology
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2523-3106
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2523-3106
DOI
10.1186/s42358-019-0090-8
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Abstract

Background: To determine the burden of Rheumatoid Arthritis (RA) on patients’ work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. Methods: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. Results: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. Conclusions: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control. Keywords: Rheumatoid arthritis, Quality of life, Work performance, Surveys, Latin America Introduction population, and this prevalence varies from 0.4 to 1.6% Rheumatoid Arthritis (RA) is an autoimmune disease in Latin America population [7–9]. that causes chronic inflammation and proliferation in Since RA is not curable, the goals of RA therapy are to the synovial tissue of joints, leading to cartilage damage reach disease remission or to achieve low disease activity and joint destruction [1–3]. Irreversible damage occurs [10, 11]. Aggressive treatment in early RA has shown to early and continue throughout the patient’s life [4–6]. reduce functional disability over time, and positively in- RA affects approximately 1% of the United States (US) fluence employment [12, 13]. Lack of optimal control leads to joint damage and loss of physical function, work impairment, and finally permanent work disability. Un- * Correspondence: rxavier10@gmail.com 1 ceasing joint injury and irreversible loss of physical func- Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil tioning will negatively impact patients’ work Full list of author information is available at the end of the article performance and/or employability. A recent study © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Xavier et al. Advances in Rheumatology (2019) 59:47 Page 2 of 11 showed that work disability rates increases in accordance Item Work Limitations Questionnaire (WLQ-25), 36- to disease duration: 35, 39, and 44% after 5, 10, and 15 Item Short Form Health Survey (SF-36) and EuroQol 5 years of RA diagnosis, respectively [14]. Dimensions Questionnaire 3 level version (EQ-5D-3 L). There is still a need of detailed information on how All standardized questionnaires were adequately trans- RA patients are successful on preserving employability lated into Brazilian Portuguese and Spanish. Some of the and how is the current burden of RA on work product- instruments had already been validated with final ver- ivity in Latin America. sions reported in previous publications or by their copy- Therefore, this study primarily aimed to determine the right holders. [16–20] The remaining questionnaires and burden of RA on patients’ work productivity and health versions were validated within the scope of the study, related quality of life (HRQoL) and to explore the im- using usual methods in the field. pact of related variables. Additionally, the progression of RA and its impact on work productivity and HRQoL Work productivity were also investigated. WALS is a 12-item questionnaire that assesses patient’s limitation at work without a recall period. Answers op- Methods tions consist of a 4-point Likert scale that ranges from 0 Study design and eligibility criteria (no difficulties) to 3 (not able to do). Dimensions in- PROSE RA study (Patient Reported Outcomes Survey of cludes difficulty getting to and from work, lifting, work- Employment among patients with RA) is an inter- ing with hands, crouching/bending/kneeling/reaching, national multicenter prospective survey. Patients were work pace, concentration, standing/sitting for long pe- included from May/2012 to September/2015 in 18 riods, and meeting work demands. Overall score ranges rheumatology public and private clinics from four Latin from 0 to 36 points and higher measures indicate greater American countries: Argentina, Brazil, Colombia and limitation [21]. Mexico. All sites in Argentina, Colombia and Mexico WPAI:RA contains six questions to measure disabil- were private, while 2 out of 3 Brazilian sites were pub- ities in paid and unpaid work in the last seven days. Re- licly funded. Patients diagnosed with RA identified in sults include four scores that summarize the percentage outpatient routine visits were invited to participate and of: work time missed due to health; impairment while were included if they met the eligibility criteria: Age be- working due to health; activity impairment due to tween 21 and 55 years (representing a working age health; and Overall work impairment score due to health group); documented diagnosis of RA as defined by the problems. The scores ranges from 0 to 100 points and revised 1987 classification criteria of the American Col- higher measures indicate greater limitation in each do- lege of Rheumatology (ACR) [15]; and willing to provide main [22]. informed consent to participate in the study. Patients WLQ-25 is composed by 25-items and focuses on not able to give informed consent and/or to complete presenteeism and the proportion of work-time with limi- the study procedures were excluded. Two different ana- tation as opposed to the degree of difficulty or severity lyses were performed: cross-sectional to determine the of limitations. It assesses four dimensions of presentee- burden of RA on patients’ work productivity and ism while at work: physical demands, time management, HRQoL (primary) considering the baseline answers to mental-interpersonal demands and output demands. selected patient-reported outcomes (PROs), and longitu- Questions regarding work productivity and performance dinal over 1 year to evaluate the progression of RA and over the past 2–4 weeks were answered using a 5-point its impact on work productivity and HRQoL Likert scale, ranging from 0 (none of the time) to 4 (all (secondary). of the time). Each scale was scored separately and scores were converted from 0 to 100, where higher scores rep- Data collection resent increased limitations [23, 24]. Five study visits were performed every three months over 1-year follow-up. During each visit, participants an- Health-related quality of life swered an interview that assessed data about sociodemo- SF-36 is a composed by 36 questions grouped into 8 do- graphic and clinical characteristics, lifestyle behavior, mains (physical functioning, role-physical, bodily pain, disease activity, use of Disease-Modifying Antirheumatic general health, vitality, social functioning, role- Drugs (DMARDs), direct medical resource utilization emotional, and mental-health). Two summary measures and medication coverage/insurance. Impact on work are also provided: Physical Component Summary (PCS) productivity and HRQoL was evaluated using standard- and Mental Component Summary (MCS). The raw score ized instruments: Workplace Activity Limitation Scale of each dimension was converted into a value from 0 (WALS), Work Productivity and Activity Impairment (worst possible health state) to 100 (best possible health Questionnaire - Rheumatoid Arthritis (WPAI:RA), 25- state). All scales were standardized to the 1998 general Xavier et al. Advances in Rheumatology (2019) 59:47 Page 3 of 11 US population using the norm base scale algorithm. normal distribution using the Shapiro-Wilk and Scale score < 45 can be interpreted as being below the Kolmogorov-Smirnov tests. To compare means, vari- average range for the general population [25]. ables with normal distribution were analyzed by the Stu- EQ-5D-3 L assesses health status through 5 domains dent’s t-test and those with non-normal distribution by (mobility, self-care, usual activities, pain/discomfort and Mann-Whitney or Wilcoxon nonparametric tests. Linear anxiety/depression) considering 3 levels: no problems, regression was used to build a multivariate model to as- some problems, extreme problems. Additionally, a Vis- sess the association between outcomes and exposure ual Analogue Scale (EQ-VAS) records respondents’ self- variables, controlled for possible confounders and inter- rated health from “Best imaginable health state”=0 to actions. Due to the small sample size for each country, “Worst imaginable health state”=100. Utility score repre- bivariate and multivariate analyses were performed con- sents a scale between death = 0 and perfect health = 1 sidering the entire sample only. Analysis of the impact and is derived from the answers to each dimension, cal- of disease progression (longitudinal) on work productiv- culated using the United Kingdom algorithm [26, 27]. ity and HRQoL was assessed through the difference on mean scores between study visits 1 and 5. Thus, these Disease progression differences are shown and tested among disease progres- Multi-Dimensional Health Assessment Questionnaire sion groups: “Improvement or maintenance” and (MDHAQ) was used in the first and last visits to evalu- “Worsening”. ate disease activity, which is a 4-domains measure: phys- Only valid answers were used for all PROs. Guidelines ical function (FN), pain (PN), Rheumatoid Arthritis [21, 23, 25, 26, 28] from each standardized instruments Disease Activity Index (RADAI) and patient global esti- report different strategies to deal with missing data as mate (PTGL). Final disease activity measure was ob- follows: MDHAQ (if at least one question left un- tained using Rheumatology Assessment Patient Index answered in any domain, patient excluded from this spe- Data 3 measures (RAPID3), calculated from the answers cific analysis); WALS (patient excluded from specific of three MDHAQ domains (FN, PN and PTGL). analysis, if more than two questions left unanswered; RAPID3 score ranges from 0 to 30 points and classify values estimated through the mean of answered data, if patients into four groups: remission (≤3 points), low se- until two questions left unanswered or the answer of any verity (3.1 to 6 points), moderate severity (6.1 to 12 question “refused”); WPAI:RA (questionnaires with points) and high severity (> 12 points) [28]. Disease pro- missing answers did not have the corresponding score gression was defined as disease activity modification dur- calculated); WLQ (patient excluded from specific ana- ing the study period, considering the interval between lysis if > 2 questions were left unanswered); SF-36 (miss- the first and last visits, classified in the following cat- ing values estimated through the mean of answered data egories: Improvement or maintenance; and Worsen. in the same scale for patients with responses for at least half of the domain questions); and EQ-5D-3 L (patient Sample size calculation excluded of specific analysis, if any question left PROSE RA study was primarily designed to assess how unanswered). RA impacts on work productivity and HRQoL at base- Stata (version MP12) and R Project (version 3.2) were line and also to analyze association with exposure vari- adopted to perform the analysis with a 95% confidence ables. Thus, sample size was calculated based on interval and p-value≤0.05. assumptions of potential differences between these groups from published data [20, 29–32]. Simulations for Ethical approval a descriptive approach were performed to assure an ad- Research was reviewed and approved by Independent equate precision of estimated parameter using two dif- Ethics Committee according to study site and respon- ferent margins of error: a score difference observed by sible committees are listed in Additional file 1: Table S1. each subgroup and a fixed value of 5.0% of the max- All procedures were in accordance with the ethical stan- imum in each scale. Considering ɑ = 0.05 and a power of dards from each country and with the Helsinki declar- 0.80 and adopting a conservative approach, the higher ation and its later amendments or comparable ethical estimated sample size was select (N = 280) assuring that standards. Written informed consent and authorization the study would have power to detect the smallest to use and/or disclose his/her anonymised health data difference. was obtained from all participants. Statistical analysis Results Descriptive analysis was performed through means and Sociodemographic and clinical characteristics standard deviation to quantitative variables, and fre- The study enrolled 290 patients at baseline: 75 (25.9%) quency to qualitative variables. Data were tested for from Argentina, 75 (25.9%) from Mexico, 72 (24.8%) Xavier et al. Advances in Rheumatology (2019) 59:47 Page 4 of 11 from Colombia and 68 (23.4%) from Brazil. Sociodemo- 95%CI = 12.10 to 19.72; p < 0.001). The “absenteeism and graphic and clinical characteristics are shown in Tables 1 presenteeism” category was decreased by: medication and 2. coverage/insurance (β = − 2.70; 95%CI = -4.95 to − 0.45; NA = Not applicable. p = 0.021) and consultations in the last 3 months (β = − RA = Rheumatoid Arthritis. 1.26; 95%CI = -2.40 to − 0.11; p = 0.033). Having per- SD = Standard Deviation. formed ancillary tests in the last 3 months (β = 1.27; DMARDs = Disease-Modifying Antirheumatic Drugs. 95%CI = 0.19 to 2.53; p = 0.023) and previous orthopedic RA = Rheumatoid Arthritis. surgery (β = 1.80; 95%CI = 0.32 to 3.22; p = 0.019) in- RAPID3 = Rheumatology Assessment Patient Index creased “absenteeism and presenteeism”. Impairment in Data 3 measures. regular daily activities was decreased by overweight/ SD = Standard Deviation. obesity (β = − 7.14; 95%CI = -14.03 to − 0.25; p = 0.042); and increased by disease activity (β = 19.47; 95%CI = Work productivity at baseline 16.67 to 22.28; p < 0.001) and female group (β = 12.14; Table 3 shows descriptive analysis of WALS, WPAI:RA 95%CI = 1.08 to 23.21; p = 0.032). and WLQ-25. Results stratified in accordance with ex- For the total sample, WLQ-25 physical demands scale posure variables for total sample and final models for (40.3%) was the most affected due to RA, ranging from each questionnaires’ measures are shown in Additional 44.0% in Mexico to 35.5% in Colombia. Productivity loss file 1: Tables S2 and S3, respectively. represented by WLQ-25 index was 7.0% (SD = 5.1), ran- RA = Rheumatoid Arthritis. ging from 7.8% (SD = 5.6) in Colombia to 5.9% (SD = SD = Standard Deviation. 4.5) in Brazil. In multivariate final model, higher educa- WALS=Workplace Activity Limitation Scale. tional levels - technical or trade school to complete post- WLQ-25 = 25-item Work Limitations Questionnaire. graduate education - (β = − 0.36; 95%CI = -0.70 to − 0.02; WPAI:RA = Work Productivity and Activity Impair- p = 0.039) and having undergone a previous orthopedic ment Questionnaire - Rheumatoid Arthritis. surgery (β = − 0.50; 95%CI = -1.00 to − 0.01; p = 0.045) Overall mean WALS score in total sample was 9.0 decreased productivity losses. (SD = 6.1), ranging from 8.2 (SD = 6.3) in Mexico to 10.6 (SD = 6.8) in Brazil. At least 40.3% of RA patients re- Health-related quality of life ported some disability in each of the WALS questions. Table 4 shows descriptive analysis of HRQoL measures. Main limitations informed in the workplace were diffi- These measures were stratified in accordance with ex- culty to crouch, bend, kneel or work in awkward posi- posure variables for total sample and final model for tions (84.0%) and to lift, carry or move objects (80.1%). each of the questionnaires’ measures are shown in Add- A similar pattern was observed among participating itional file 1: Tables S4 and S5. countries. Multivariate analysis showed that higher work EQ-5D-3 L = EuroQol 5 Dimensions Questionnaire 3 limitation according to WALS was observed when pa- level version. tients had medication coverage/insurance (β = 2.35; MCS = Mental Component Score. 95%CI = 0.21 to 4.50; p = 0.031) and increased disease PCS=Physical Component Score. activity level (β = 3.67; 95%CI = 3.01 to 4.34; p < 0.001). RA = Rheumatoid Arthritis. Employment was reported by 60.3% of the total re- SD = Standard Deviation. spondents of WPAI:RA - 72.6% in Argentina, 62.5% in SF-36 = 36-Item Short Form Health Survey. Colombia, 57.3% in Mexico and 44.2% in Brazil (data Considering data for general population, seven of not shown). Considering total sample, the ability to per- eight scales from SF-36 questionnaire in total sample form usual activities due to RA was the mostly affected have shown scores slightly below the reference value category (42.5%; SD = 30.9), and presenteeism was the (lower limit: 45). Value observed in the scale “Vitality” most impaired productivity dimension (29.5%; SD = for total sample was the only within the range of 45 28.8). All participating countries had a comparable pat- and 55. The same pattern was observed in each of tern. In WPAI:RA final multivariate model, having previ- the countries, with the exception of Mexico, that has ous orthopedic surgery (β = − 1.80; 95%CI = -3.28 to − shown scores within the range for the scales “Vitality” 0.31; p = 0.020), medication coverage/insurance (β = − (49.8; SD = 10.3) and “Mental Health” (46.7; SD = 2.69; 95%CI = -4.99 to − 0.39; p = 0.024) and consulta- 11.6). All PCS measures were below the reference tions in the last 3 months (β = − 1.22; 95%CI = -2.39 to − value for total sample and also for each country. 0.05; p = 0.042) decreased absenteeism; while reporting Mean estimated for MCS was above reference value having performed ancillary tests increased (β = 1.27; for total sample, and also in Brazil and Mexico. In 95%CI = 0.19 to 2.53; p = 0.023). Each disease activity themultivariateanalysis, patients whohad performed level significantly increased presenteeism (β = 15.91; ancillary tests in the last 3 months had a decrease in Xavier et al. Advances in Rheumatology (2019) 59:47 Page 5 of 11 Table 1 Description of studied sociodemographic characteristics among RA patients at baseline Characteristic Argentina Brazil Colombia Mexico Total (N = 75) (N = 68) (N = 72) (N = 75) (N = 290) N% N% N% N% N% Age [Mean/SD] 43.4 7.8 45.9 6.8 49.3 8.9 41.6 9.5 43.7 8.4 Gender Female 68 90.7 59 86.8 64 88.9 70 93.3 261 90.0 Race Mestizo NA NA 15 22.1 45 62.5 72 96 132 45.6 Caucasian/White 37 49.3 36 52.9 3 4.2 NA NA 76 26.2 Hispanic/Latin 37 49.3 NA NA 21 29.2 NA NA 58 20.0 African American NA NA 14 20.6 1 1.4 –– 15 5.2 Brazilian Indian NA NA 1 1.5 NA NA NA NA 1 0.3 Native American NA NA NA NA 1 1.4 NA NA 1 0.3 Other NA NA 2 2.9 NA NA NA NA 2 0.7 Marital Status Married 41 54.7 35 51.5 30 41.7 41 54.7 147 50.7 Single/Not ever married 20 26.7 19 27.9 24 33.3 18 24.0 81 27.9 Partner/Common law 8 10.7 4 5.9 11 15.3 5 6.7 28 9.7 Divorced 2 2.6 5 7.4 1 1.3 7 9.3 15 5.2 Separated 4 5.3 –– 3 4.2 1 1.3 8 2.8 Widowed –– 3 4.3 3 4.2 2 2.7 8 2.7 Educational level Incomplete High School 18 24.0 32 47.1 15 20.8 6 8.0 71 24.5 Complete High School 17 22.7 18 26.5 12 16.7 17 22.7 64 22.1 Technical or trade school NA NA 5 7.4 16 22.2 20 26.7 41 14.1 Complete or incomplete graduate degree 35 46.7 4 5.8 20 27.8 18 24.0 77 26.6 Complete postgraduate 2 2.6 4 5.8 9 12.5 4 5.3 19 6.6 Primary occupation Professional or technical 16 21.3 4 5.9 18 25.0 13 17.3 51 17.6 Office worker 13 17.3 3 4.4 13 18.1 4 5.3 33 11.4 Service worker 9 12.0 10 14.7 11 15.3 7 9.3 37 12.8 Sales 7 9.3 2 2.9 6 8.3 6 8.0 21 7.2 Manager, official or proprietor 4 5.3 1 1.5 6 8.3 5 6.7 16 5.5 Craftsman or foreman 2 2,7 2 2.9 2 2.8 1 1.3 7 2.4 Operative 1 1.3 3 4.4 3 4.2 1 1.3 8 2.8 Other 12 16.0 6 8.8 11 15.3 34 45.3 69 21.7 NI 11 14.7 37 54.4 2 2.8 4 5.3 54 18.6 Smoking habit Nonsmokers 40 53.3 39 57.4 47 65.3 51 68.0 177 61.0 Former smokers 22 29.3 17 25.0 20 27.8 12 16.0 71 24.5 Current smokers 13 17.4 12 17.6 5 6.9 11 14.7 41 14.2 the PCS score (β = − 2.33; 95%CI = -4.17 to − 0.49; p = 6.21; p < 0.001) and MCS, in at least 3.34 points (β = 0.013); and each category of disease activity, from re- − 3.34; 95%CI = -4.72 to − 1.96; p < 0.001). mission to high severity, decreased the score of PCS, EQ-VAS mean score ranged from 64.4 (SD = 21.5) in in at least 7.06 points (β = − 7.06; 95%CI = -7.87 to − Brazil to 75.4 (SD = 21.6) in Mexico and for the whole Xavier et al. Advances in Rheumatology (2019) 59:47 Page 6 of 11 Table 2 Description of studied clinical characteristics among RA patients at baseline Characteristic Argentina Brazil Colombia Mexico Total (N = 75) (N = 68) (N = 72) (N = 75) (N = 290) N % N% N% N% N% Clinical characteristics Body Mass Index [Mean/SD] 26.8 4.9 29.2 6.1 24.8 3.7 27.6 5.2 27.0 5.3 Comorbidities 53 70.7 59 86.8 40 55.6 40 53.3 192 66.2 Patients who underwent at least one previous orthopedic surgery 18 24.0 12 17.6 11 15.3 7 9.3 48 16.6 Disease characteristics Disease duration (years) [Mean/SD] 8.9 9.0 10.8 6.7 8.6 7.3 7.7 7.2 9.0 7.7 Time since symptoms onset (years) [Mean/SD] 9.7 9.0 12 7.8 9.5 7.3 9.4 7.4 10.1 8.0 Patients with medication coverage/insurance 68 90.7 47 69.1 69 95.8 55 73.3 239 82.4 Use of DMARDs 66 88.0 60 88.2 62 86.1 69 92.0 260 89.7 Disease activity (RAPID3 score) Remission 9 12.0 3 4.4 6 8.3 15 20.0 33 11.4 Low severity 17 22.7 1 1.5 9 12.5 11 14.7 38 13.1 Moderate severity 14 18.7 23 33.8 21 29.2 21 28.0 79 27.2 High severity 22 29.3 38 55.9 31 43.1 22 29.3 113 39.0 Direct medical resource utilization in the last three months Patients with at least one outpatient visit 58 77.3 52 76.5 58 80.5 56 74.7 224 77.2 Patients with at least one visit to perform tests 47 62.7 48 70.6 45 62.5 49 65.3 196 67.9 Patients who underwent at least one surgery (any type) 4 5.3 1 1.5 4 5.6 1 1.3 10 3.4 sample was 69.8 (SD = 20.4). Mean utility score was 0.67 observed between these measures (p =0.270). How- (SD = 0.23) for total sample and ranged from 0.62 (SD = ever, the majority of patients (79.4%) has improved or 0.19) to 0.71 (SD = 0.23) among countries. Final multi- maintained the disease activity level during the 1-year variate model for EQ-VAS has shown that patients with follow-up period. a longer disease duration (≥9 years) (β = − 5.19; 95%CI = Considering differences between the first and last -9.52 to − 0.85; p = 0.019) and presenting worsening of study visits, worsening in the disease activity showed an disease activity level (β = − 10.74; 95%CI = -12.81 to − association with an increase on impact on work product- 8.68; p < 0.001) have a decrease in the score. Beside this, ivity and HRQoL. Patients who had improvement/main- use of DMARDs increased EQ-VAS score (β = 8.39; tenance had also an improvement in the assessed 95%CI = 1.52 to 15.25; p = 0.020). measures and those who worsened also had a worsening Regarding utility scores from EQ-5D-3 L instrument, in the scores, except for WLQ-25. However, a statisti- ancillary test multivariate analysis indicates that over- cally significant difference was observed only for WALS weight/obese patients (β = − 0.06; 95%CI = -0.11 to − (p = 0.001); WPAI:RA domains “presenteeism” (p = 0.003; p = 0.039) and those with a longer disease 0.020) and “impairment of regular daily activities” (p = duration (≥9 years) (β = − 0.05; 95%CI = -0.10 to − 0.01; 0.017); components of SF-36: physical (p < 0.001) and p = 0.012) have a decrease in the utility score. Utility mental (p < 0.001); and EQ-5D-3 L utility score (p = score is also reduced with the increase of the disease ac- 0.007) - Table 5. tivity level (β = − 0.12; 95%CI = -0.14 to − 0.10; p < EQ-5D-3 L = EuroQol 5 Dimensions Questionnaire 3 0.001). On the other hand, mestizos patients showed an level version. increasing in utility scores (β = 0.06; 95%CI = 0.01 to HRQoL = Health-Related Quality of Life. 0.11; p = 0.010). WALS=Workplace Activity Limitation Scale. WLQ-25 = 25-item Work Limitations Questionnaire. Disease progression and impact on work productivity and WPAI:RA = Work Productivity and Activity Impair- HRQoL ment Questionnaire - Rheumatoid Arthritis. It was observed a slightly higher mean of RAPID3 SD = Standard Deviation. score in Visit 1 (10.7; SD = 6.6) than in Visit 5 (9.7; SF-36 = 36-Item Short Form Health Survey. SD = 6.7), but no statistical significant difference was VAS=Visual Analogue Scale. Xavier et al. Advances in Rheumatology (2019) 59:47 Page 7 of 11 Table 3 Work productivity assessed through WALS, WPAI:RA and WLQ-25 questionnaires among RA patients at baseline Work Productivity Argentina Brazil Colombia Mexico Total Mean SD Mean SD Mean SD Mean SD Mean SD WALS N =52 N =22 N =64 N =68 N = 206 1.Get to and from work and maintain punctuality [N/%] 18 34.6 11 50.0 30 46.9 24 35.3 83 40.3 2. Getting to the workplace [N/%] 26 50.0 11 50.0 43 67.2 36 52.9 116 56.3 3. Sitting for long periods of time at your job [N/%] 17 32.7 10 45.5 38 59.4 34 50.0 99 48.1 4. Standing for long periods of time at your job [N/%] 34 65.4 15 68.2 49 76.6 46 67.6 144 69.9 5. Lift, carry or move objects [N/%] 39 75.0 18 81.8 52 81.3 56 82.4 165 80.1 6. Working with your hands [N/%] 35 67.3 17 77.3 45 70.3 30 44.1 127 61.7 7. Crouching, bend, kneel or work in awkward positions [N/%] 43 82.7 20 90.9 52 81.3 58 85.3 173 84.0 8. Stretch out [N/%] 33 63.5 19 86.4 40 62.5 37 54.4 129 62.6 9. With the schedule of hours of work that your job requires [N/%] 18 34.6 12 54.5 30 46.9 30 44.1 90 43.7 10. With the pace of work that your job requires [N/%] 27 51.9 12 54.5 37 57.8 42 61.8 106 51.5 11. Meet your current job demands [N/%] 25 48.1 14 63.6 36 56.3 37 54.4 110 53.4 12. To concentrate and keep your mind on your work [N/%] 19 36.5 12 54.5 7 10.9 25 36.8 92 44.7 Overall score of WALS (0–36) 8.4 5.6 10.6 6.8 9.7 6.0 8.2 6.3 9.0 6.1 WPAI:RA N =73 N =52 N = 72 N =75 N = 272 Normal Daily Activities % Daily activity impairment due to RA 34.0 28.2 56.1 27.4 46.7 29.0 36.5 33.8 42.5 30.9 Professional Activities % Impairment while working due to RA (presenteeism)* 23.9 23.9 32.6 26.8 40.5 32.2 23.1 28.5 29.5 28.8 % Work time missed due to RA (absenteeism)* 12.0 27.5 5.8 23.5 7.5 21.6 8.4 18.8 9.0 23.2 % Overall work impairment due to RA (absenteeism and presenteeism)* 10.3 25.0 5.9 23.9 7.6 21.9 8.9 20.3 8.6 22.6 WLQ-25 N =59 N =36 N =43 N =53 N = 191 % work impairment due to physical demands 41.1 24.7 37.7 24.1 35.5 24.0 44.0 28.7 40.3 21.4 % work impairment due to time demands 33.5 24.7 29.3 30.6 32.4 26.8 27.9 29.0 30.9 28.0 % work impairment due to output demands 27.6 24.4 18.1 19.3 29.9 25.8 22.7 23.3 24.9 23.8 % work impairment due to mental-interpersonal demands 20.1 21.9 15.2 18.0 20.9 24.8 16.1 20.1 18.2 23.8 WLQ-25 index (%) 7.5 5.1 5.9 4.5 7.8 5.6 6.5 4.9 7.0 5.1 Discussion presenteeism, indicating that patients are working with Our sample was comprised of patients from 4 Latin reduced performance and which seems to lead to un- American countries, mostly middle-aged, female, from employment [33–36]. For example, WPAI presenteeism multiethnic origin, married with a technical or profes- measure (percentage of impairment while working due sional occupation. The educational level was well- to RA) in our sample was 28.8%, while healthy controls distributed in the total sample, but Brazilian patients in a previous study in Sweden reported a mean impair- had a higher frequency of incomplete or complete high ment of 20.9%. [37] Regarding HRQoL, physical aspect school only. This observation may be at least partially of the disease seems to be the major impairing condition explained by the type of funding for study sites in the [38–41]. Although these available data, there are several sample, once only Brazil had publicly-funded healthcare standard PROs that assess these outcomes from different services enrolling patients and those facilities usually at- perspectives, and this study analyzed a unique RA popu- tend people with lower income and lower educational lation using these different instruments. level in the country. Our results about burden of RA on work productivity The burden of RA on Latin-American patients’ work assessed at baseline demonstrated an important impact productivity and HRQoL was comprehensively assessed of the disease on patients’ life, related to several dimen- using standard PROs. Thus, it was possible to descrip- sions according to the instrument, and corroborate tively compare these data with findings from other con- international data that patients are working with reduced texts and countries. In summary, RA was related with performance. The overall work impairment due to RA at Xavier et al. Advances in Rheumatology (2019) 59:47 Page 8 of 11 Table 4 Health-related quality of life assessed through SF-36 and EQ-5D-3 L questionnaires among RA patients at baseline Health-related Quality of Life Argentina Brazil Colombia Mexico Total Mean SD Mean SD Mean SD Mean SD Mean SD SF-36 N = 75 N = 68 N = 72 N = 75 N = 290 Vitality 46.9 10.9 47.0 9.5 47.9 10.2 49.8 10.3 47.9 10.3 Mental health 42.5 11.4 44.3 12.3 43.7 10.4 46.7 11.6 44.3 11.5 Social functioning 41.9 11.6 40.1 11.3 40.6 11.5 44.2 10.9 41.8 11.4 Bodily pain 43.2 10.7 36.6 8.3 39.3 10.1 43.5 10.7 40.8 10.4 Role physical 42.4 11.5 37.0 11.5 39.1 10.7 43.0 9.7 40.5 11.1 General health 41.9 9.7 38.5 11.9 39.5 8.9 41.6 12.2 40.4 10.8 Role emotional 39.9 13.9 41.2 13.5 37.5 11.6 42.1 11.3 40.2 12.7 Physical functioning 38.5 11.0 32.0 8.6 37.6 10.6 40.2 12.2 37.2 11.1 Mental Component Score (MCS) 43.4 11.9 47.3 11.9 43.9 9.9 47.2 11.3 45.4 11.3 Physical Component Score (PCS) 41.8 9.8 33.6 9.6 38.7 9.1 41.5 10.7 39.1 10.3 EQ-5D-3 L N=73 N=68 N =70 N =75 N = 286 Overall Value (0–100) 71.5 16.6 64.4 21.5 67.4 20.2 75.4 21.6 69.8 20.4 Utility Score (0–1) 0.67 0.25 0.62 0.19 0.66 0.25 0.71 0.23 0.67 0.23 baseline in our sample was similar or lower than the ob- When HRQoL was assessed at baseline, a major im- served in previous studies, depending on the characteris- pact on physical aspects was observed, with lower phys- tics of studied sample [33–35]. The work limitations ical SF-36 score (when compared with mental score), as related to presenteeism were also investigated using described in the literature. EQ-VAS value estimated in WALS measures and our patients are classified as our study was 69.8 (SD = 20.4), which is similar to those having high severity of work place disability [36]. In reported for Brazilian RA patients (mean score: 63 to the present study, all WLQ-25 subscales at baseline 74) [43], and different from Mexican patients (mean were higher than results observed in US populations score: 49.5) with osteoarthritis, RA or chronic low-back of RA patients. A remarkable difference is noted in pain [44]. Utility measure calculated was 0.67 and no physical demands scale, indicating that Latin Ameri- studies describing utility among Latin American RA pa- can patients are more limited in work environment tients were found to date. This measure is usually used mainly in this scale [38, 42]. to define public health policies, resource allocation and Table 5 Comparison between differences in work productivity and HRQoL scores and disease progression from the first to the last study visit Outcomes Disease Progression Improvement or maintenance Worsening p-value Mean Difference SD Mean Difference SD Work Productivity WALS −0.9 4.1 1.9 4.2 0.001 WPAI:RA Absenteeism −0.7 25.3 5.0 14.7 0.118 Presenteeism −3.7 24.9 11.0 21.2 0.020 Absenteeism and Presenteeism −0.9 26.7 5.0 14.8 0.101 Impairment of regular daily activities −5.5 28.4 7.0 27.0 0.017 WLQ-25 0.4 7.3 −0.2 8.1 0.723 HRQoL SF-36 PCS 2.9 7.1 −1.7 7.1 < 0.001 MCS 1.1 10.3 −4.0 6.6 < 0.001 EQ-5D-3 L Overall VAS Value 5.2 22.8 −1.4 17.7 0.142 Utility score 0.03 0.25 −0.06 0.18 0.007 Xavier et al. Advances in Rheumatology (2019) 59:47 Page 9 of 11 evaluation of services and programs, as it works as a observation suggests that this is a particularly refractory proxy of how people value changes in health status [45], population or that the management could be subopti- highlighting the need for these studies in Latin America. mal. Further analyses of the data, including medication It is known that multiple factors act to generate work use, will be done to address this issue. impairment and poor HRQoL [46]. Obesity, living with- The aforementioned associations of HRQoL and work out partner, being mestizo, the presence of comorbidi- productivity among different stratum of study popula- ties, having medication insurance/coverage, longer tion were not yet well established and, thus, more stud- disease duration, having performed ancillary test and ies are needed in order to infer a causal relationship [14, consultations and a previous orthopedic surgery were as- 40, 46, 48–53]. However, it is important that healthcare sociated with a worsening in work productivity and/or professionals stay alert to those characteristics during HRQoL. An improvement in the assessed PROs scores RA patients’ management and also patients, families and was associated with a higher educational level, having the society, with the aim to minimize its effects on pa- medication insurance/coverage, being mestizo, having tients’ professional and personal lives. It is worth men- recently performed ancillary test and consultations, a tioning that health systems should be investing in history of previous orthopedic surgery and use of strategies and technologies targeting disease activity con- DMARDs. Some variables behaved as protective or risk trol among RA patients, once this seems to be a variable factors, depending on the instrument assessed, suggest- strongly related to higher burden not only to patients, ing that these relationships still needs to be further ad- but also the society. The data presented here will cer- dressed. Also, unexpectedly, obesity and overweight tainly be useful to better estimate the cost-effectiveness were associated with reduced impairment in regular of these treatment strategies, invaluable information for daily activities in the WPAI analysis, as compared to optimizing the use limited health resources in relatively underweight/normal BMI values. This finding seems in low-income countries, particularly nowadays with the conflict with our observation that obese/overweight indi- growing number of costly anti-rheumatic drugs viduals have worse quality of life (EQ-5D-3 L utility available. score) and could not be explained by our data. A similar This was the first study conducted in countries from pattern was observed for the association between greater Latin America with the aim to assess RA patients work work limitations according to WALS and medication productivity and HRQoL. This study adds knowledge in coverage/insurance. Potential confounders not collected an area scarcely studied and improves global disease in our study may play in this association. comprehension about burden of RA in Latin America. With exception of WLQ-25, all PROs were associated with disease activity. The hypothesis that the disease ac- tivity may have a great impact in these aspects of pa- Conclusion tients’ life arises from the presence of joint damage and This study highlights the importance of regular and loss of physical function in RA, which seems to be a timely disease management for RA patients, specially fo- prognostic factor in the ability to keep or get a new job cusing on the need to decrease disease activity to pro- [14, 47]. This relationship was also observed in the mote better results in PROs. An increase in disease longitudinal analysis, and confirms the finding from activity was responsible for a significant decrease in cross-sectional analysis showing that disease worsening HRQoL, and a significant increase in workplace disabil- is associated with an increase of the impact on work ities, leading to a more difficult time in maintaining or productivity and a decrease of HRQoL scores. Although seeking job opportunities. Also, multiple factors were no studies in the literature have assessed this relation- identified that seem to be associated with work impair- ship over time, this finding corroborates the main goals ment and HRQoL, but as for the protective factors, fur- proposed by EULAR (The European League Against ther research is still needed. This study’s results Rheumatism) and ACR (American College of Rheuma- highlight the need for a more comprehensive and holis- tology) – o since the disease is not entirely curable, RA tic approach to RA management and that all relevant therapy must aim to reach disease remission, and if it is stakeholders (from families to HR managers) should be not possible, to achieve low disease activity reflecting on aware of RA’s burden in patients’ everyday life. Also, it patients’ professional and personal lives [10, 11]. About sheds some light in a subject that is often overlooked, this aspect, it is important to notice that in the studied adding to the evidence that the burden of RA in QoL is population, most patients had moderate or high disease significant. Finally, the knowledge of the burden of dis- activity at baseline and maintained it during the 1-year ease in Latin America is often limited, and this study follow-up. Considering the recommendations for strat- contributes to the ever-increasing need to raise aware- egies of close monitoring and prompt therapy adjust- ness so that resource allocation is focused on tackling ments to achieve low disease activity or remission, this this issue. Xavier et al. Advances in Rheumatology (2019) 59:47 Page 10 of 11 Supplementary information Competing interests Supplementary information accompanies this paper at https://doi.org/10. The authors declare that they have no competing interests. 1186/s42358-019-0090-8. Author details Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Additional file 1: Table S1. Independent Ethics Committee/Institutional Alegre, Porto Alegre, Brazil. Centro Paulista de Investigações Clínicas (CEPIC), Review Board approvals. Table S2. Work productivity assessed through São Paulo, Brazil. Universidade Federal de São Paulo, São Paulo, Brazil. WALS, WPAI:RA and WLQ-25 questionnaires among several exposure 4 5 Morales Vargas Centro de Investigación, Guanajuato, Mexico. Fundación groups of RA patients at baseline. Table S3. Final model for the associ- Instituto de Reumatología Fernando Chalem, Bogotá, Colombia. Centro ation between work productivity (WALS, WPAI:RA and WLQ-25 scores) Integral de Reumatología – Reumalab, Medellín, Colombia. Centro de and exposure groups at baseline. Table S4. Health-related quality of life Investigaciones en Enfermedades Reumáticas (CIER), Buenos Aires, Argentina. assessed through SF-36 and EQ-5D-3L questionnaires among several ex- 8 9 Desarrollos Biomédicos y Biotecnológicos, Monterrey, Mexico. Circaribe, posure groups of RA patients at baseline. Table S5. Final model for the Barranquilla, Colombia. CEIM Investigaciones Medicas, Buenos Aires, association between health-related quality of life (SF-36 and EQ-5D-3L Argentina. Instituto Médico Especializado (IME), Buenos Aires, Argentina. scores) and exposure groups at baseline. 12 13 AbbVie Farmacêutica Ltda, São Paulo, Brazil. Unidad de Investigación en Enf. Crónico-Degenerativas, Guadalajara, Mexico. Abbreviations Received: 1 November 2018 Accepted: 21 October 2019 ACR: American College of Rheumatology; DMARDs: Disease-Modifying Antirheumatic Drugs; EQ-5D-3 L: EuroQol 5 Dimensions Questionnaire 3 level version; EQ-VAS: EQ Visual Analogue Scale; FN: Physical function; HRQoL: Health related quality of life; MCS: Mental Component Summary; References MDHAQ: Multi-Dimensional Health Assessment Questionnaire; PCS: Physical 1. Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Component Summary; PN: Pain; PROs: Patient-reported outcomes; PROSE RA Drug Discov. 2003;2:473–88. study: Patient Reported Outcomes Survey of Employment among patients 2. Choy EH, Panayi GS. 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