Abstract
Objective
Early treatment of RA improves clinical outcomes; however, the impact on health economic outcomes is unclear. This review sought to investigate the relationship between symptom/disease duration and resource utilization/costs and the responsiveness of costs following RA diagnosis.
Methods
A systematic search was performed on Pubmed, EMBASE, CINAHL and Medline. Studies were eligible if patients were DMARD-naïve and fulfilled 1987 ACR or 2010 ACR/EULAR RA classification criteria. Studies had to report symptom/disease duration and resource utilization or direct/indirect costs as health economic outcomes. The relationships between symptom/disease duration and costs were explored.
Results
Three hundred and fifty-seven records were identified in a systematic search; nine were eligible for analysis. The mean/median of symptom/disease duration in studies ranged between 25 days and 6 years. Annual direct costs of RA following diagnosis showed a U-shaped distribution in two studies. Longer symptom duration before starting a DMARD (>180 days) was associated with lower health-care utilization in the first year of RA diagnosis in one study. Annual direct and indirect costs 6 months before RA diagnosis were higher in patients with shorter symptom duration (<6 months) in one study. Given the clinical and methodological heterogeneities, the association between symptom/disease duration and costs after diagnosis was not computed.
Conclusion
The association between symptom/disease duration at the time of DMARD initiation and resource utilization/cost in patients with RA remains unclear. Health economic modelling with clearly defined symptom duration, resource utilization and long-term productivity is vital to address this evidence gap.
Keywords: RA, early diagnosis, direct/indirect costs, health economic outcomes
Key messages.
The association between symptom/disease duration before DMARD initiation and health economic outcomes in RA is unclear.
Clinical and methodological heterogeneities impede direct comparison of health economic outcomes across RA studies.
Longitudinal studies with defined symptom duration and long-term RA-associated costs will address this research question.
Introduction
The impact of early treatment on clinical outcomes in RA is well reported [1]. However, the impact of early treatment on health economic outcomes is less clear. Patients with RA treated with intensive DMARD were more likely to stay in the workforce long term [2, 3]. This might result long term in overall lower indirect costs (i.e. lower loss of productivity). However, diagnostic decisions are vulnerable to false-positive and false-negative results. The consequence of over-diagnosis and over-treatment might lead to overall higher direct costs (i.e. higher medical costs) in the longer run, which might offset the cost savings made from improved productivity. Therefore, long-term economic diagnostic and treatment decision models are required to inform the optimal threshold for diagnostic/treatment decisions from an economic perspective. This will facilitate the estimation of long-term RA-related costs.
Therefore, as a first step, the relationship between symptom/diagnosis duration at the time of DMARD initiation and subsequent resource utilization/costs needs to be identified. We sought to investigate this through a systematic review of cost-of-illness and cost-effectiveness studies of DMARD-naïve RA patients.
Methods
The full Methods section is detailed in Supplementary Data S1, available at Rheumatology Advances in Practice online.
Protocol and registration
The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO 2017 CRD42017077593); https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017077593.
Study identification/search strategy
PubMed, EMBASE, CINAHL and Medline electronic databases were searched up to 25 January 2023. All systematic searches were conducted using the same search terms and strategy (Supplementary Data S2, available at Rheumatology Advances in Practice online). Additional records were identified through independent manual database searching, external sources and reference scanning of relevant retrieved full-text articles. Study selection, data extraction and quality assessment were done independently by two authors (I.S. and R.S.); discrepancies were resolved by consensus or through a third reviewer (A.Bo.). Table 1 shows the PICOT framework.
Table 1.
PICOT framework to capture studies cost or resource utilization as an outcome by symptom or disease duration in patients with DMARD-naïve RA
| Population | DMARD-naïve RA |
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| Intervention | Any DMARDs |
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| Comparator | Any other DMARD treatment |
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| Outcome | Direct costs Medication costs Indirect costs Productivity costs Resource use |
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| Time | Duration immediately preceding study inclusion or DMARD start or the period following it |
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| Context | Disease or symptom duration in relationship to the costs/resources |
PICOT: patient, intervention, comparison, outcome and time.
Study selection
Study inclusion criteria were as follows: aged ≥18 years and fulfilling the 1987 ACR or 2010 ACR/EULAR RA classification criteria; DMARD-naïve; symptom/disease duration reported; cross-sectional and longitudinal study; and health economic outcomes reported as costs or resource utilization. Studies excluded were studies of non-RA inflammatory arthritides and conference abstracts, systematic reviews and review articles.
Data extraction
The following data were extracted: study characteristics; potential determinants of RA costs; sources of resource utilization and costs; and health economic outcomes.
Quality assessment
The Strengthening The Reporting of Observational Studies in Epidemiology (STROBE) checklist [4] and a modified checklist by Drummond and Jefferson [5] were used for quality assessment.
Data synthesis and statistical analysis
A meta-analysis/regression on the association between disease/symptom duration and costs could not be performed owing to the number of studies and methodological heterogeneity, especially in reporting of health economic outcomes. Cost data per patient per year for the reported duration in studies were recorded and summarized in a unifying currency of US Dollars 2021 after adjusting for the Purchasing Power Parity (PPP) and Consumer Price Index (CPI) 2021 [6, 7].
Results
Nine articles were included in this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart shows the literature search results (Fig. 1).
Figure 1.
PRISMA flow chart of the four searches conducted. CINAHL: The Cumulative Index to Nursing and Allied Health; EMBASE: Excerpta Medica Database; MEDLINE: Medical Literature Analysis and Retrieval System Online
Table 2 summarizes study characteristics, cost categories and annual costs in international USD 2021. Six papers were cost-of-illness studies [8–13] and the remainder cost–utility studies [14–16]. Four studies were observational studies [8, 11, 13, 16] and five randomized controlled trials (RCTs) [9, 10, 12, 14, 15].
Table 2.
Study characteristics, health economic outcomes and annual costs in US Dollars 2021
| Author country, year | ObjectiveStudy designStudy setting | Patient characteristicsSymptom duration | OutcomeStudy perspective | Results as resources or costs by category (e.g. days hospitalized) or type (total health care; productivity) | Results as total resources or cost in local currency at time of the study | Cost per person per year in USD 2021 after adjusting for purchasing power parity and consumer price index 2021 (OECD, 2021) [1, 2] | |
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Total health-care (drugs and monitoring) cost per patient per year adjusted to USD 2021: 1008 | |
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Objective: estimation of:
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Outcome:
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Collaborating in the Utrecht RA cohort study group.
Pyramid, i.m. gold, MTX or HCQ.
n = 330 arthralgia patients recruited.
Median (range).
Outcome data were split into four groups based on HAQ: group 1 (HAQ = 0 at baseline and 6 months); group 2 (HAQ > 0 at baseline, 0 at 6 months); group 3 (HAQ ≥ 0 at baseline, >0 but <1.0 at 6 months); and group 4 (HAQ ≥ 0 at baseline, ≥1.0 at 6 months).
Subtotal of medical cost includes costs owing to contacts with health-care workers, days spent in care facilities, medication, monitoring for side effects and alternative medicine. Subtotal of non-medical direct cost includes costs of adaptations in the home, devices and other costs.
HCA= mean productivity per day over a 5-year follow-up was calculated for each patient and multiplied by the cumulative number of their days off work to yield the patients' loss of productivity by the HCA. FCA= estimation of loss of productivity, with the assumption that someone replaces the disabled worker after the friction period, that the initial production level is restored, and that production losses are confined to the friction period. RA-related work disability days were obtained from the official register, divided by the duration (in years) of follow-up during which the patient had not retired owing to other diseases or because of age. All final cost column states the cost per person per year in USD 2021 after adjusting for purchasing power parity and Consumer Price Index 2021.
GP: general practitioner; IQR: interquartile range; RCT: randomized controlled trial; TCZ: tocilizumab; USD: US dollars.
Sociodemographic and clinical characteristics of patients are summarized in Supplementary Table S1, available at Rheumatology Advances in Practice online. Cost categories, source of cost reference and results in local currency are summarized in Supplementary Table S2, available at Rheumatology Advances in Practice online.
The symptom, disease or diagnosis duration variables reported at baseline varied. Two studies reported symptom duration [8, 14], six studies disease duration [9–13, 16] and one diagnosis duration [15]. Only one study clearly defined symptom duration: ‘first onset of joint swelling’ [11]. The remaining studies did not state the definitions of symptom, disease or diagnosis duration [8–15].
Resource utilization and cost data across studies were heterogeneous (Table 1). Three studies reported costs (i.e. monetary value) but not resource utilization [13, 15, 16]. One study reported resource utilization without monetary values [8]. Three studies reported resource utilization and costs [10, 12, 14]. Two studies reported costs data as loss of productivity costs [9, 11].
Direct medical costs were reported in six studies (two observational studies [13, 16] and four clinical trials [10, 12, 14, 15]). Two studies reported direct non-medical costs [10, 12]. Health-care utilization with no monetary value was reported in one study [8].
Loss of productivity (indirect cost) was recorded in four studies [9, 11, 14, 15]. Two studies calculated productivity loss using the human capital and friction cost approach [9, 15]. One study used only the human capital approach [11], and one study used only the friction cost approach [14].
Study perspective refers to the point of view adopted in the economic evaluations [17], i.e. who pays for the cost. Common study perspectives are the patient, health-care system or society. Three studies reported societal perspectives (i.e. health-care and productivity loss costs) [13–15]. Two studies reported a partial societal perspective (productivity loss costs) [9, 11], and two studies reported costs from the health-care perspective [8, 16]. In addition, two studies reported both health-care (direct medical costs) and patient perspectives [10, 12].
Quality assessment has been included in Supplementary Data S3 and Table S3, available at Rheumatology Advances in Practice online.
Narrative synthesis
Luurssen-Masurel et al. [14] performed a cost–utility study in seronegative RA patients in the Rotterdam Early Arthritis Cohort (tREACH) trial. The median symptom duration was 134 days [interquartile range (IQR) 95–205 days]; follow-up duration was 1 year. Initial treatment strategies were MTX (iMTX) 25 mg once weekly, HCQ (iHCQ) 400 mg daily or a tapering course of oral glucocorticoids (iGC). There was no significant difference in the mean cumulative health-care costs over 1 year for treatment with iMTX, iHCQ and iGCs (Table 2). The difference in productivity costs over 1 year between the three groups was mainly attributed to different levels of presenteeism (Table 1). After adjusting for PPP and CPI 2021, mean total costs (health-care and productivity costs) by treatment strategy groups in USD 2021 were $14 485, $14 988 and $14 044 for the iMTX, iHCQ and iGC groups, respectively. The association between symptom duration and health-care/productivity costs in the overall cohort or by treatment groups was not assessed.
Verhoeven et al. [15] reported a 5-year cost–utility analysis of an RCT comparing tocilizumab (TCZ) plus MTX or TCZ monotherapy with MTX monotherapy in DMARD-naïve early RA patients. The median (IQR) symptom duration by treatment groups was 25 (16–42) days, 26 (18–45) days and 27 (15–46) days for the TCZ plus MTX, TCZ and MTX groups, respectively. Cumulative 5-year productivity cost loss [by human capital approach (HCA)] was highest in the TCZ plus MTX group (€51 700; n = 106) compared with the TCZ monotherapy and MTX monotherapy groups [€39 900; n = 103 and €46 500, n = 108 respectively]. Cumulative 5-year productivity cost loss (HCA) was highest in the TCZ plus MTX group (€51 700) compared with the TCZ monotherapy and MTX monotherapy groups (€39 900 and €46 500, respectively). After adjusting for PPP and CPI 2021, total direct health-care-related costs (mean) in USD 2021 at the end of year 1 were $15 546, $8350 and $17 840 per patient for the TCZ plus MTX, TCZ and MTX groups, respectively. The association between symptom duration and health-care or productivity costs in the overall cohort or by treatment groups was not assessed.
Syngle et al. [16] reported RA-related health-care costs in a single-centre prospective observational study of 3 months in India. The study assessed the cost-effectiveness of synthetic DMARDs in DMARD-naïve RA patients [16]. The mean disease duration was 5.78 years (s.d. 4.84 years). Costs reported were the average total direct medical cost per prescription per month over the 3-month study period. This figure equates to 997.05 Indian Rupees per patient. After adjusting for PPP and CPI 2021, the average (extrapolated) annual direct medical costs at the end of year 1 in USD 2021 was $1008 per patient. The association between disease duration and direct medical costs was not assessed.
Kuijper et al. [8] compared health-care utilization between arthralgia and DMARD-naïve early RA patients at baseline, 6 and 12 months in a Dutch inception observational cohort study [8]. The median symptom duration for RA patients was 103 days (range 7–373 days). Use of DMARDs was not reported. A longer (>180 days) vs short symptom duration (90–180 days) at baseline was associated with lower levels of health-care utilization over 12 months [Incidence Ratio Rate of 0.65 (95% CI 0.50, 0.85, P = 0.002)]. The mean number of visits to medical specialists peaked at 6 months in the RA group (Table 2). However, a decrease in overall health-care visits (i.e. general practitioner, medical specialist, physiotherapist and alternative health practitioner visits) was observed following diagnosis (Table 2). No monetary value was reported in this study. In summary, longer symptom duration (>180 days) was associated with lower health-care utilization over the first year of diagnosis.
Puolakka et al. [9] assessed the impact of the Stanford Health Questionnaire (HAQ) index on loss of productivity in early DMARD-naïve RA patients in the Finnish RA Combination Therapy (FIN-RACo) open-label extension clinical trial in Finland. Patients were randomized to either a combination of three DMARDs (SSZ, MTX and HCQ) and prednisolone, or a single DMARD with or without prednisolone [9] for 2 years and were followed up for 5 years. The mean disease duration across the four HAQ groups was between 8 and 11 months. In the overall cohort and over 5 years, the annual mean loss of productivity per patient was €8344 (95% CI 6516, 10 480) by the HCA and €1928 (95% CI 1567, 2298) by the friction cost approach (FCA). Functional capacity was assessed by HAQ at baseline and 6 months. The HAQ score after 6 months of treatment, but not the level of HAQ at baseline, predicted productivity costs in the overall cohort. Over 5 years, the top HAQ quartile had the highest work disability days per year [mean 273 days (95% CI 194, 328)], compared with the lowest HAQ quartile [mean 34 days (95% CI 5, 145)]. After adjusting for PPP and CPI 2021, the annual mean loss of productivity in USD 2021 in the top quartile group was $40 116 by the HCA method and $6125 by the FCA method. No analysis was performed to assess the impact of disease duration on costs in the overall cohort or by HAQ groups.
Verstappen et al. [10] assessed the total annual direct costs over different follow-up periods after first DMARD in Dutch patients with RA and identified sociodemographic, clinical and psychological predictors of high costs in two RCTs. Patients in the first RCT were randomized into one of four treatment arms [pyramid (NSAID followed by a DMARD for treatment failure), i.m. gold, MTX or HCQ]. Patients from the second RCT were randomized into intensive vs conventional MTX regimes. In this study, costs data were classified into three groups with increasing follow-up duration after diagnosis (0 to ≤2 years, 2 to ≤6 years and 6 to ≤10 years). In addition, RA patients with disease duration ≥10 years from the Utrecht RA Cohort study group were included to capture costs data for patients with longstanding RA. There was a significant difference in annual direct costs between the four groups. The median annual direct costs per patient showed a U-shaped distribution, i.e. costs were high for patients with follow-up duration 0 to ≤2 years (€2923) and reduced after 2–6 years (€1967), but increased again for ≥10 years follow-up duration (€3778). Data from the group with the shortest follow-up duration were extracted for Table 1. Functional disability (HAQ) was the most important variable associated with high costs after adjusting for sociodemographic, clinical and psychological variables. After adjusting for PPP and CPI 2021, the annual mean (median) of total direct costs per patient in USD 2021 was $14 613 ($8159). The annual direct costs of early RA follow a U-shaped distribution over 10 years following the start of DMARDs. No analysis was performed to assess the impact of disease duration at baseline on costs in the overall cohort.
Merkesdal et al. [11] reported the magnitude of indirect costs, changes within cost components and the correlation between changes in cost and social, clinical and occupational variables within first 3 years for DMARD-naïve RA patients in a multicentre observational study in Germany. The average indirect cost in early RA at the 24-month follow-up was high; $11 750 per person-year (US dollars for the period 1994–1996), which related to 126 days of loss of productivity. Loss of productivity owing to sick leave accounted for 84% of overall loss of productivity (sick leave, work disability and other work loss) between the onset of disease and the end of the first year after study enrolment, compared with only 25% at the end of the second year of the study enrolment [11]. After adjusting for PPP and CPI 2021, the mean costs associated with total sick leave, work disability and other work losses in USD 2021 were $20 180 after 12 months of follow-up and $18 848 per person per year at the 24-month follow-up time point. The relationship between disease duration and loss of productivity was not reported.
Newhall-Perry et al. [13] assessed the direct and indirect costs of seropositive RA patients 6 months before diagnosis in a longitudinal observational study at rheumatology centres in the western USA and Mexico. All patients were DMARD-naïve and had clinically active disease, with at least nine tender and six swollen joints and a positive RF. Patients were classified as disease duration of <6 months (n = 87) and ≥6 months (n = 63). At baseline, the mean total direct costs and indirect costs of RA 6 months before diagnosis were $200 per month and $281 per month in 1994 USD, respectively. The total direct costs of RA [mean (s.d. )] 6 months before diagnosis in patients with disease duration <6 months compared with ≥6 months were $240/month ± $285 and $144/month ± $149, P < 0.001, respectively. Likewise, indirect costs were higher in patients with a disease duration <6 months as opposed to ≥6 months ($348/month ± $567 vs $188/month ± $506; P < 0.005) at baseline. After adjusting for PPP and CPI 2021, the annual mean total direct and indirect costs 6 months before diagnosis per person in USD 2021 were $12 663 for <6 months and $7174 for ≥6 months groups. Overall, annual direct and indirect costs 6 months before RA diagnosis were higher in patients with shorter symptom duration (<6 months).
van Jaarsveld et al. [12] assessed the annual direct cost related to RA during the first 6 years and identified socioeconomic and clinical determinants of these costs in an RCT conducted in the Netherlands. Patients were recruited between 1990 and 1996, and cost questionnaires were sent to those not lost to follow-up in April 1996. Mean annual direct costs by follow-up duration (year 1–6) followed a U-shaped distribution, as follows: Dutch florin (Dfl.) 14 455/patient in year 1; Dfl.13 800/patient in year 2; Dfl. 9457/patient in year 3; Dfl. 6233/patient in year 4; Dfl. 13 005/patient in year 5; and Dfl. 11 158/patient in year 6. After adjusting for PPP and CPI 2021, total direct costs per patient (mean) in USD 2021 were $24 094 after 1 year follow-up duration. The annual direct costs of early RA showed a U-shaped distribution over 6 years following the start of DMARDs. No analysis was performed to assess the impact of disease duration at baseline on costs in the overall cohort.
A number of studies were excluded because study participants could receive at least one DMARD before study enrolment [18–21]. Tables 3 and 4 summarize the direct and indirect costs in USD 2021, respectively, and outcomes by increasing symptom or disease duration.
Table 3.
Direct costs in USD 2021, symptom duration and outcomes according to increasing symptom or disease duration
| Author, country, year | Symptom or disease duration | Symptom or disease duration (days) | Currency in USD 2021 | Outcome |
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| Verhoeven et al. [15] The Netherlands, 2021 |
Symptom duration | Median: TCZ+MTX 24.5 TCZ 25.5 MTX 27.0 |
Mean: TCZ + MTX 15 546 TCZ 18 350 MTX 17 840 |
Direct health-care-related costs by treatment strategy group, per patient per year |
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| Luurssen-Masurel et al. [14] The Netherlands, 2021 |
Symptom duration | Median: 134 | Mean: iMTX 3456 iHCQ 2839 iGC 4079 |
Healthcare costs by treatment strategy group, patient per year |
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| Verstappen et al. [10] Netherlands, 2004 |
Disease duration | Mean: 329 | Mean: 14 613 Median: 8159 |
Total direct costs per patient per year |
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| van Jaarsveld et al. [12] The Netherlands, 1998 |
Disease duration | Inclusion criteria: 0–365 | Mean: 16 472 | Direct medical cost per person per year, per patient |
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| Syngle et al. [16] India, 2017 |
Disease duration | Mean: 2117 | Average: 1008 | Direct medical cost per patient per year |
iGC: initial treatment strategy with glucocorticoids; iHCQ: initial treatment strategy with HCQ; iMTX: initial treatment strategy with MTX; TCZ: tocilizumab.
Table 4.
Indirect costs in USD 2021, symptom duration and outcomes according to increasing symptom or disease duration
| Author, country, year | Symptom or disease duration | Symptom or disease duration (days) | Currency in USD 2021 | Outcome |
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| Merkesdal et al. [11] Germany, 2001 |
Disease duration | Mean: 213 | Mean: Time 0–time 2: 20 180 Time 2–time 3: 15 865 Time 0–time 3: 18 848 |
Loss of productivity costs: total sick leave, work disability and other work loss |
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| Luurssen-Masurel et al. [14] The Netherlands, 2021 |
Symptom duration | Median: 134 | Mean: iMTX 11 031 iHCQ 12 149 iGC 9967 |
Total productivity costs by treatment strategy group |
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| Verhoeven et al. [15] The Netherlands, 2021 |
Symptom duration | Median: TCZ+MTX 24.5 TCZ 25.5 MTX 27.0 |
Human capital approach: TCZ + MTX 17 076 TCZ 14 272 MTX 16 566 Friction cost approach: TCZ + MTX 6371 TCZ 5862 MTX 6371 |
Loss of productivity costs loss using human capital approach and friction cost approach by treatment strategy group |
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| Puolakka et al. [9] Finland, 2009 |
Disease duration HAQ group 1 |
Mean: 335 |
Mean: HCA 736 FCA 590 |
Loss of productivity cost by human capital approach and friction cost approach by HAQ group |
| HAQ group 2 | 243 | HCA 4523 FCA 2275 |
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| HAQ group 3 | 243 | HCA 20 191 FCA 4101 |
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| HAQ group 4 | 304 | HCA 40 116 FCA 6125 |
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iGC: initial treatment strategy with glucocorticoids; iHCQ: initial treatment strategy with HCQ; iMTX: initial treatment strategy with MTX; TCZ: tocilizumab; time 0: onset of disease; time 2: reassessment at 12 months following baseline assessment; time 3: reassessment at 24 months following baseline assessment.
Discussion
This study highlighted several interesting findings. Firstly, two studies reported a U-shaped distribution of costs over disease duration following an RA diagnosis. Total costs were high during the initial years, slightly lower thereafter, then high again for a disease duration of ≥5 years [12] and >10 years [10]. This indicates that costs are not a linear function of disease duration.
Secondly, functional disability was a predictor of productivity costs in three studies [9, 10, 12]. In one study, patients from the highest HAQ group had the highest work disability days per year, hence the highest costs for loss of productivity [9]. This finding is highly relevant. It supports the hypothesis that aggressive early treatment can reduce costs in the longer term, because those treated earlier are less likely to have a higher level of disability, which then translates to a lower loss of productivity costs in the long term.
One study reported that the annual direct and indirect costs 6 months before diagnosis were higher in those with a symptom duration of <6 months before the start of DMARD therapy compared with those with a symptom duration ≥6 months [13]. In contrast, another study reported that longer symptom duration before diagnosis (>180 days) was associated with lower health-care utilization over the first year of diagnosis [8]. The contrasting trend between the two studies can be explained by the difference in the timing of when the health economic outcomes were recorded. Health-care utilization over the first year following RA diagnosis was recorded in the latter study; however, costs before RA diagnosis were recorded in the former study.
In this review, we could not delineate the aggregated-level data related to the relationship between symptom/disease/diagnosis duration and cost categories owing to the heterogeneity of the following factors: timing and duration of data collection regarding resources and costs; type of resources/cost-categories reported; and inconsistency in reported disease, symptom or diagnosis duration (Fig. 2). Moreover, the duration of cost data recorded (i.e. 6 months vs 6 years) also differed across studies (Fig. 2).
Figure 2.
Timing and duration for which the respective health economic outcomes are reported and the symptom duration before DMARD initiation. The blue arrows indicate the symptom/disease duration reported in each study. The green arrows indicate the timing and duration of health economic outcomes reported in each study. Puolakka et al. [9] reported six groups of patients stratified by HAQ groups. aVerstappen et al. [10] reported four groups of patients based on disease duration (defined as the time elapsed from study recruitment). Van Jaarsveld et al. [12] reported six groups of patients based on disease duration (defined as the time elapsed from study recruitment). bKuijper et al. [8] and Newhall-Perry et al. [13] reported disease duration at the time of study enrolment. FCA: friction cost approach; HCA: human capital approach
Before the era of early treatment, RA costs were related to established disease. Patients had more frequent hospitalization [22] and more frequent joint replacement than the general population [23], and a majority were unable to work. The early introduction of biological and targeted synthetic DMARD therapy has resulted in high costs of medications [23]. However, high drug cost can potentially be offset in the long term, at least in part, by reducing disease-related costs (e.g. loss of productivity owing to work disability, hospitalization and joint surgery). In addition, patients treated early were more likely to achieve DMARD-free remission [1]. Therefore, this would reduce the proportion of patients on long-term DMARDs [24].
Clear definitions of RA onset and duration have been proposed [25], because reporting in clinical studies is currently heterogeneous [25]. RA duration can be timed from the following points: onset of RA symptoms; onset of joint swelling; when RA classification criteria were first fulfilled; or the time of RA diagnosis. Using a clearly defined onset will allow meaningful comparison of clinical outcomes and health economic outcomes between early RA studies.
A strength of this review is the broad range of health economic outcomes and types of health economic studies that were included. Both direct and indirect costs, and cost-of-illness and cost-utility studies were within the scope of this review. Observational and clinical trials were also included.
However, only a small number of studies fulfilled our strict inclusion criteria. In addition, studies that enrolled patients who had recently been treated with DMARDs before study recruitment were not included in this review. Furthermore, meta-analyses/regression were not possible owing to the different types of health economic outcomes reported.
This review is the first to highlight a vital evidence gap in early arthritis: what is the financial consequence of diagnosing and treating patients with RA during the early disease phase? Health economic modelling with carefully defined symptom duration, resource utilization, treatment and long-term productivity costs is vital to address this important question.
Supplementary Material
Acknowledgements
We wish to thank Stephen Yates and Jennifer Manders, University Hospitals Birmingham Foundation NHS Trust, who conducted the systematic search for this review.
Contributor Information
Ilfita Sahbudin, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.
Ruchir Singh, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK; Department of Rheumatology, Sandwell and West Birmingham NHS Trust, Birmingham, UK.
Jeanette Trickey, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.
Aliaksandra Baranskaya, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.
Alexander Tracy, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.
Karim Raza, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK; Department of Rheumatology, Sandwell and West Birmingham NHS Trust, Birmingham, UK.
Andrew Filer, Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK.
Sue Jowett, Health Economics Unit, Institute for Applied Health Research, University of Birmingham, Birmingham, UK.
Annelies Boonen, Division of Rheumatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.
Supplementary material
Supplementary material is available at Rheumatology Advances in Practice online.
Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
Funding
This work was supported by the National Institute for Health and Care Research (NIHR)/Wellcome Trust Clinical Research Facility and NIHR Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust. This work was also supported by the Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (Arthritis Research UK grant number 20298), the European Community's Collaborative project FP7-HEALTH-F2-2012–305549 ‘Euro-TEAM’ and Versus Arthritis Research into Inflammatory Arthritis Centre (Versus Arthritis UK grant number 22072). The views expressed are those of the author(s) and not necessarily those of the MRC or Arthritis Research UK. I.S. is supported by the University of Birmingham via a clinical lectureship. K.R. and A.F. are supported by the NIHR Birmingham Biomedical Research Centre.
Disclosure statement: K.R.: Personal fees from Abbvie and Sanofi; grant/research support from Bristol Myers Squibb. A.F.: Personal fees from Abbvie, Roche and Janssen; grant/research support from Roche, UCB, Mestag, GSK and Janssen. The remaining authors have declared no conflicts of interest.
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Data Availability Statement
The data underlying this article will be shared on reasonable request to the corresponding author.