Area of Residence and Socioeconomic Factors Reduce Access to Biologics for Rheumatoid Arthritis Patients in Romania Cstslin Codreanu,1,2Claudiu C…. [628159]

Research Article
Area of Residence and Socioeconomic Factors Reduce Access to
Biologics for Rheumatoid Arthritis Patients in Romania
Cstslin Codreanu,1,2Claudiu C. Popescu ,1,2and Corina Mogo Gan1,2
1“Dr. Ion Stoia” Clinical Center for Rheumatic Diseases, 5th Thomas Masaryk Street, District 2, 020983 Bucharest, Romania
2“Carol Davila” University of Medicine and Pharmacy, 37th Dionisie Lupu Street, District 1, 030167 Bucharest, Romania
Correspondence should be addressed to Claudiu C. Popescu; [anonimizat]
Received 20 December 2017; Accepted 29 March 2018; Published 8 May 2018
Ac
ademic Editor: Ewa Mojs
Copyright © 2018 C ˘at˘alin Codreanu et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Introduction . The study aimed to evaluate the influence of socioeconomic factors on rheumatoid arthritis (RA) patients’ access
to biologics in Romania. Method . Cross-sectional data were collected in January 2014 from the Romanian Registry of Rheumatic
Diseases (RRRD) comprising all RA patients on biologics from 42 Romanian counties. “Territorial” access to biologics was defined
by patients receiving biologics in their home county. A county was “equitable” if <25% of RA patients received biologics outside
it.Results . The RRRD included 4507 RA patients aged 56.7 ± 12.1 years, with a disease duration of 12.1 ± 8.3 years. Urban
dwellers (67 .8%) had a significantly higher prevalence of territorial biologic access than rural dwellers (83.1% compared to 74.1%;𝑝 < 0.001). Gross domestic product (GDP) in 1000 €/capita/county (odds ratio (OR) = 1.224) and number of physicians/1000inhabitants/county (OR = 2.198) predict territorial access to biologics and also predict the number of territorially treated
RA patients. Inequitable counties exhibited significantly lower socioeconomic indicators than equitable counties. Conclusion .
In Romania, RA patients’ access to biologics varies significantly between counties. Urban dwellers and patients living in
counties/regions with high living standards are more likely to re ceive biologics locally than those living in more deprived areas.
1. Introduction
Rheumatoid arthritis (RA) is a systemic inflammatory auto-
immune disorder affecting approximately 1% of the generalpopulation [1]. Recent epidemiological data show an increasein disease incidence in women in the past ten years [2]. RAcan lead to functional disability, low quality of life, increasedmorbidity, and mortality [3].
Since RA usually affects professionally active people,
it has important economic consequences, adding costs to
patients and their families and to society through extensive
use of health resources and loss of work productivity [4, 5].The main goal of RA treatment is to induce and maintainremission whenever possible, or at least low disease activ-ity [6]. Biological disease modifying antirheumatic drugs(bDMARDs) have revolutionized the therapy of RA and theirefficacy is largely documented in clinical trials worldwide [7–9]. However, the high cost of bDMARDs is limiting theiruse, particularly in developing countries (since 2000, theRomanian public healthcare system reimburses adalimumab,etanercept, infliximab original and biosimilar, and rituximab,and since 2015 it also reimburses abatacept, certolizumab,golimumab, and tocilizumab).
In order to be eligible for bDMARDs in Romania, RA
patients must be nonresponders to two different conventionalsynthetic DMARDs (csDMARDs) just like in other Europeancountries, but they must fulfill other severity criteria whicha r es t r i c t e r[ 1 0 ] .W h i l es o m eE u r o p e a nc o u n t r i e sd on o treimburse bDMARDs yet, others offer free prescription,regardless of disease duration and previous therapies [10].In 2011, among Central and Eastern European countries,Romania had the fifth highest prevalence of bDMARDstreatment among RA patients (2.2%) [11]. This variation ofbDMARD uptake in Europe is coupled with observationalevidence that socioeconomic status, area of residence, andincome influence disease activity, disease outcome, and treat-ment access [12–15], which shows that significant inequities
exist among different European countries with respect to RA
Hindawi
BioMed Research International
Volume 2018, Article ID 7458361, 8 pages
https://doi.org/10.1155/2018/7458361

2 BioMed Research International
management. Therefore, it is reasonable to hypothesize that
these same limiting factors also create inequities at a nationallevel especially because the regions of Romania differ interms of socioeconomic and development characteristics. TheRomanian territory is divided into 4 macroregions, 2 regions,and 42 counties: macroregion 1 consists of the Northwest
(6 counties) and Center (6 counties) regions; macroregion 2
consists of Northeast (6 counties) and Southeast (6 counties)regions; macroregion 3 consists of South (6 counties) andCapital (2 counties) regions; macroregion 4 consists ofSouthwest (5 counties) and West (4 counties) regions. His-torically and economically, macroregions 1 and 3 are the mostdeveloped areas of Romania, while macroregions 2 and 4 aresignificantly below the European Union’s mean. This unevendistribution could hypothetically generate similar differencesregarding access of RA patients to expensive medication(biologics). In this context, the study aims to evaluate theinfluence of socioeconomic factors on RA patients’ access tobiological therapy in Romania.
2. Materials and Methods
2.1. Romanian Eligibility Criteria for bDMARD Therapy in RA.In order to be considered for bDMARDs therapy, RomanianRA patients must fulfill four criteria: (a) the diagnosis of RAto be be made by a rheumatologist and it should fulfill the2010 RA classification criteria [16]; (b) either high diseaseactivity (HDA) irrespective of disease duration or earlyRA (under 2 years) with moderate disease activity (MDA)a n dw i t ha tl e a s tfi v ep o o rp r o g n o s i sf a c t o r s ,b o t hw i t ha t
least 5 swollen and/or tender joints and at least two of the
following three criteria: morning stiffness above 60 minutes,erythrocyte sedimentation rate (ESR) above 28 mm/h, and Creactive protein (CRP) more than 3 times the upper limit ofnormal (ULN); (c) lack of response to at least two csDMARDsused for 12 weeks each; (d) no known contraindications forbDMARDs.
RA activity is assessed using the composite 28-joint count
disease activity score (DAS28), which is based on the numberof tender joints, number of swollen joints, ESR or CRP , andthe visual analog scale for patient-reported general health[17]: patients with HDA have a DAS28 >5.1, while patients
with MDA have a DAS28 >3.2.
The mentioned poor prognosis factors include age under
45 years; rheumatoid factor and/or anticitrullinated protein
antibodies 10 times the ULN; ESR >50 mm/h or CRP >5
times the ULN; erosions on X-rays, ultrasound or magnetic
resonance imaging; Health Assessment Questionnaire scoreabove 1.5; extra-articular manifestations.
2.2. The Romanian Registry of Rheumatic Diseases (RRRD).
As soon as a patient fulfills the above criteria for bDMARDs
use, the attending rheumatologist uploads the data into theRRRD, which is a national electronic database comprising
all RA patients treated with biologics in Romania. Prior to
treatment and inclusion in the RRRD, all patients signed
an informed consent form for both bDMARD therapy and
scientific use of their data.For the purpose of this study, the variables were collected
in January 2014 using a cross-sectional study design: demo-
graphics (age, sex, and area of residence) and RA-specificvariables (disease duration, bDMARDs). The geographicaldistribution of patients (Romania has 42 administrativedivisions: 41 counties and the capital) was reconfigured from
a treatment perspective: if the patient received the bDMARD
in home county, the case was considered “territorial” access;if the patient received the bDMARD outside home county,the case was considered “extraterritorial” access. Similarly, ifa county had less than 25% of its RA patients treated outside,the county was considered to have “equitable” access; if morethan 25% of its RA patients were treated outside, the countywas considered to have “inequitable” access. The local andRRRD ethics committees approved the study protocol.
2.3. Socioeconomic Indicators. Socioeconomic indicators
were collected from the National Institute of Statistics
Yearbook (EUROSTAT [18]) and included the populationdistribution by county, indicators of living standards: grossdomestic product (GDP) per capita per county in localcurrency (Romanian Leu) and Euro, physicians’ distributionnationwide and by county, and the rheumatologists’distribution per counties.
2.4. Statistical Analysis. The normal distribution of the data
was assessed using descriptive statistics, normality and stem-
and-leaf plots, and the Lilliefors corrected Kolmogorov-Smirnov test. The age of the patients and their diseaseduration were distributed normally and therefore they werereported as “mean ±standard deviation.”
On a patient-based analysis (4507 patients), the associa-
tion between residence (rural or urban) and bDMARD access(territorial and extraterritorial) was assessed using a 𝜒
2test
with a Cramer’s 𝑉statistic for effect size. The differences
between continuous variables (age, GDP , number of physi-cians, and number of rheumatologists) between patients withterritorial or extraterritorial biologic access were assessedusing𝑡-tests. Effect size for these 𝑡-tests was calculated by
Cohen’s𝑑statistic, approximated by running the 𝑡-tests
using the standardized values ( 𝑍scores) of the independent
variables and observing the mean difference output of these𝑡-tests. A binary logistic regression model was computed inorder to predict the likelihood that RA patients will haveterritorial bDMARD access using the following predictors:age (years), area of residence (coded “0” for rural and “1”
for urban), GDP (expressed in 1000 €/capita/county) and
number of physicians/1000 inhabitants/county. The resultswere reported in terms of odds ratios (OR) with 95%confidence intervals (CI).
On a county-based analysis (42 counties), GDP/capita,
number of physicians/1000 inhabitants, and number ofrheumatologists/county exhibited a nonnormal distribution;therefore the differences of these scale variables accordingto type of county (equitable and inequitable) were stud-ied using Mann–Whitney tests (effect size for these testswas evaluated by estimating Glass rank biserial correlationsusing bivariate Spearman’s correlations between the nominala n ds c a l ev a r i a b l e s ) .F o rt h es a m er e a s o n ,t h ec o r r e l a t i o n s

BioMed Research International 3
14.6%66.9%5.6%0.4%21.3%1.1%6.9%27.8%17.1%15.8%73.1 %9.9%72.9%56.3%8.4%0.0%49.4%9.7%68.2%24.2%87.9%
200 400 600 0
number of RA patients treated with biologicsabagarbbcbhbnbrbtbvbzcjclcsctcvdbdjgjglgrcounty
territorialextraterritorial
(a)6.2%3.6%91.6%90.0%2.2%55.3%6.7%6.1%11.5%51.6%29.3%1.9%5.0%6.7%24.0%60.0%2.9%61.5%65.9%14.6%6.8%
territorialextraterritorial100 200 300 400 0
number of RA patients treated with biologicshdhrifilismhmmmsntotphsbsjsmsvtltmtrvlvnvscounty
(b)
Figure 1: The distribution of RA patients treated with biologics according to county and treatment access (territorial and extraterritorial).
The percentages represent the fraction of RA patients who benefited from extraterritorial access to biologics: for example, in the capital (“b”,
(a)), there were 693 RA patients on biologics, but only 3 (0.4%) were treated extraterritorially, while in other counties more than 90% were
treated extraterritorially. Counties are designated by their Romanian abbreviation.
between these scale variables among themselves and with
the number of territorially and extraterritorially treatedRA patients per county were computed using Spearman’srho coefficients. Two hierarchical multiple linear regressionmodels were constructed in order to predict the numberof RA patients with territorial access to biologics. Bothmodels used GDP/capita as predictor in the first step. For thesecond step, in the first model the number of physicians/1000inhabitants was added as predictor, while in the secondmodel the number of rheumatologists/county was added as
predictor. These predictors were previously normalized by
extracting square roots (number of rheumatologists/county)or by calculation of their natural logarithms (number ofphysicians/1000 inhabitants). Since the number of physiciansand the number of rheumatologists are not independentvariables (the number of physicians includes the numberof rheumatologists), they were not included together in thesame regression model.
The statistical tests were considered significant if 𝑝<
0.05. All the statistical analysis was done using IBM SPSSStatistics version 22.0 for Windows (Armonk, NY, IBMCorp.).
3. Results
3.1. Patient-Based Analysis. Until January 2014, the RRRD
included 4507 patients with RA: 4267 (94.7%) treated withbiologics and 240 (5.3%) with approved biological therapy,but treatment not yet started. The patients had a meanage of56.7 ± 12.1 years and a mean RA duration of
12.1±8.3 years. The majority of patients were women (3842
patients—85.2%) and the majority of patients lived in urbanareas (3056 patients—67 .8%). In the sample, 80.2% (3614) ofRA patients benefited from territorial bDMARD access, while19.8% (893) had extraterritorial bDMARD access (Figure 1,Table 1). Urban dwellers had a significantly higher prevalenceof territorial bDMARD access than rural dwellers (Figure 2).
Compared to RA patients with territorial bDMARD
access, those with extraterritorial bDMARD access had
equivalent mean ages but came from counties with signifi-
cantly lower socioeconomic indicators (Figure 3).
The logistic regression model ( 𝜒
2(5)=1018.9;𝑝<0.001)
explained 32.1% of bDMARD accessibility (Nagelkerke 𝑅2=
0.321) and it correctly classified 81.7% of patients. Account-ing for all other predictors included/present in the model,GDP expressed in 1000 €/capita/county (OR = 1.224; 95%CI: 1.186–1.263) and number of physicians/1000 inhabitantsper county (OR = 2.198; 95% CI: 1.845–2.618) significantlyincreased the likelihood that patients will have (equitable)territorial bDMARD access.
3.2. County-Based Analysis. The majority of RA patients who
are treated with bDMARDs outside their home environments
chose the capital (Bucharest): 53.7% (805/1498) of patientstreated in Bucharest come from a different county. Comparedto equitable counties regarding bDMARD treatment, theinequitable counties exhibited significantly lower socioeco-nomic indicators (Figure 4).

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Table 1: Characteristics of Romanian divisions: macroregions (4), regions (8), and counties (42).
Division Inhabitants GDP Physicians Rheumatologists RA biologics
Macroregion 1 5468525 7123.2 2.45 50 872
Northwest 2834186 7049.7 2.72 32 547
Bihor 619102 5095.0 2.93 6 99
Bistrit ¸a-N˘as˘aud 329188 4503.3 1.33 2 43
Cluj 721955 6977 .6 5.08 16 201
Maramures ¸5 25765 3 809.4 1 .56 3 1 19
Satu Mare 390639 4014.1 1.52 2 45
S˘alaj 247537 4304.7 1.51 3 40
Center 2634339 7406.4 2.29 18 325
Alba 380976 5320.4 1.77 1 41
Bras¸ov 630807 6521.9 2.16 5 76
Covasna 228732 4288.3 1.70 1 43
Harghita 333674 4361.5 1.38 1 28
Mures ¸ 595948 4428.3 3.50 8 83
Sibiu 464202 6358.1 2.54 2 54
Macroregion 2 6794269 6235.8 1.68 64 1358
Northeast 3922407 4887.6 1.72 45 858
Bac˘au 746566 3899.3 1.43 3 75
Botos¸ani 455973 2922.3 1.33 2 123
Ias¸i 919049 4227.4 3.25 30 313
Neamt ¸ 577359 3118.8 1.40 4 104
Suceava 743645 3375.7 1.34 4 125
Vaslui 479815 2535.4 1.29 2 118
South-East 2871862 7161.8 1.66 19 500
Br˘aila 356196 4519.9 1.47 2 54
Buz˘au 478811 3582.4 1.19 1 63
Constant ¸a 769768 6414.3 2.62 10 203
Galat¸i 631669 3766.2 1.38 2 62
Tulcea 244249 3755.8 1.47 1 15
Vrancea 391169 3262.1 1.31 3 103
Macroregion 3 5757871 10892.3 3.22 89 1469
South 3260976 6724.4 1.38 13 633
Arges ¸ 646333 6487.6 2.11 3 103
C˘al˘aras¸i 317293 3223.0 1.00 0 48
Dˆambovit ¸a 528426 4090.3 1.23 2 81
Giurgiu 276781 3291.2 1.06 0 58
Ialomit ¸a 293658 3747.3 1.01 0 70
Prahova 809052 5828.3 1.45 7 208
Capital 2496895 18653.8 4.74 76 776
Ilfov 390751 9798.3 1.51 1 83
Bucures ¸ti 2106144 13574.6 6.02 75 693
Macroregion 4 4221053 6706.5 2.82 32 868
Southwest 2206321 5683.5 2.10 9 365
Dolj 700117 4486.8 3.02 7 175
Gorj 366261 5498.3 1.75 0 44
Mehedint ¸i 286678 3527.0 1.70 0 38
Olt 450094 3090.2 1.49 0 64
Vˆalcea 403171 4292.8 1.75 2 44

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Table 1: Continued.
Division Inhabitants GDP Physicians Rheumatologists RA biologics
West 2014732 8045.6 3.13 23 503
Arad 473946 5599.7 2.44 3 18
Caras¸-Severin 328047 4703.2 1.79 0 64
Hunedoara 469853 4742.9 2.36 5 81
Timis ¸ 742886 7938.1 4.99 15 340
Notes . Data from 2013; county names are in Romanian; for each county: GDP €/capita, number of physicians/1000 inhabitants, absolute number of
rheumatologists, and absolute number of RA patients treated with biologics. GDP: gross domestic product; RA: rheumatoid arthritis.
2,539 1,075 517 37683.1%
74.1%
25.9%16.9%p < 0.001
urban rural
habitat01,0002,0003,000number of RA patients on biologics
territorialextraterritorialtreatment access
Figure 2: Access to biologics of RA patients according to habitat:
83.1% of urban dwellers had territorial access to biologics, comparedto only 74.1% of rural dwellers ( 𝑝<0.001;𝜒
2test; effect size Cramer’s
𝑉=0.205,𝑝<0.001).
The number of rheumatologists/county, the number of
physicians/1000 inhabitants/county, and GDP/capita were
s i g n i fi c a n t l ya n dp o s i t i v e l yc o r r e l a t e dw i t ht h en u m b e ro fterritorially treated RA patients/county (rho = 0.843, 𝑝<
0.001;r h o=0 . 4 4 8 , 𝑝=0.003;r h o=0 . 3 3 7 , 𝑝=0.034,r e s p . ) ,
and they were significantly and negatively correlated with thenumber of extraterritorially treated RA patients/county (rho=−0.340,𝑝 = 0.027;r h o= −0.410,𝑝 = 0.007;r h o= −0.337,
𝑝=0.034 resp.).
The distribution of socioeconomic indicators among
counties was uneven in terms of number of rheumatolo-gists/county (mean = 5.6; median = 2.0; skewness = 4.84;kurtosis = 26.2; minimum = 0; maximum = 75), the numberof physicians/1000 inhabitants/county (mean = 2.01; median= 1.52; skewness = 2.13; kurtosis = 4.48; minimum = 1;maximum = 6.02), and GDP/capita (mean = 4824 €; median= 4299 €; skewness = 2.48; kurtosis = 8.25; minimum =2535 €; maximum = 13575 €).2.1
0.31.76.6
4.95.7 5.6
3.2
rheumatologists/county/10physicians/1000 inhabitants
GDP/capita/1000 (Euro)age/10 (years)∗ ∗
##
&&
§§
territorial extraterritorial
bDMARD access02468mean
Figure 3: Differences between RA patients with territorial or
extraterritorial access to biologics (bDMARD) regarding ageand county socioeconomic indicators (gross domestic product –
GDP/capita; number of physicians/1000 inhabitants and number
of rheumatologists). The 𝑝values represent the significance of
𝑡-tests. Effect sizes are evaluated by Cohen’s 𝑑statistics:−0.72
for rheumatologists/county, −0.89 for physicians/county; −0.51 for
GDP/capita; −0.07 for age. The variables have been scaled to
appropriate coillustration size by decimal division.
#,&,§𝑝< 0.001;
∗𝑝=0.067.
Two hierarchical regression analysis models were com-
puted to predict the number of territorially treated RA
patients using GDP (1000 €/capita/county) in the first step
and then adding either the number of physicians/1000
inhabitants/county or the number of rheumatologists/countyas predictors (Table 2). GDP on its own significantly
explained 43.4% of the variance of territorially treated RA
patients. Adding either the number of physicians/1000 inhab-itants/county or the number of rheumatologists/county pro-
duced significant models in which these variables predicted
a na d d i t i o n a l2 2 . 3 %a n d4 6 . 8 % ,r e s p e c t i v e l y ,i nt h ev a r i a n c eo f
territorially treated RA patients. In both models GDP became
an insignificant predictor when both independent variables

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rheumatologists/10physicians/1000 inhabitantsGDP/capita/1000 (Euro)3.924.39∗∗
#
1.471.74#
13
§§
equitable inequitable
type of county0246median
Figure 4: Differences between equitable and inequitable counties
regarding access to biologics in terms of socioeconomic indicators
(gross domestic product – GDP/capita; number of physicians/1000
inhabitants and number of rheumatologists). The 𝑝values represent
the significance of Mann–Whitney tests. Effect size was evaluatedusing Glass rank biserial correlation: 0.34 for GDP/capita; 0.38 for
physicians; 0.63 for rheumatologists. The variables have been scaled
to appropriate coillustration size by decimal division.
∗𝑝= 0.338,
#𝑝=0.016,a n d§𝑝<0.001.
Table 2: Hierarchical regression models predicting the number ofterritorially treated RA patients.
GDP GDP + physicians GDP + rheumatologists
𝑅20.434 0.656 0.901
𝐹 30.6 37 .3 177 .9
𝑝𝑅2<0.001 <0.001 <0.001
𝑅2change – 0.223 0.468
𝑝𝑅2change – <0.001 <0.001
𝐵 93.1 72.1 −3.7
𝑝𝐵<0.001 0.203 0.718
Notes . GDP was expressed per 1000 €/capita/county; the number of physi-
cians was expressed per 1000 inhabitants/county; the number of rheumatol-
ogists was expressed per county; there are 2 models: model 1 (GDP at the first
step, GDP and physicians at the second step); model 2 (GDP at the first step,
GDP and rheumatologists at the second step). GDP: gross domestic product;RA: rheumatoid arthritis.
( G D Pa n dn u m b e ro fp h y s i c i a n so rG D Pa n dn u m b e ro f
rheumatologists) were entered into the regression model, anobservation explained by the degree of correlations of GDPwith the number of physicians/1000 inhabitants/county (rho=0 . 7 3 1 ;𝑝 < 0.001) and with the number of rheumatolo-gists/county (rho = 0.438; 𝑝=0.004 ).4. Discussion
The aim of the study was to assess the impact of socioe-conomic factors on Romanian RA patients’ accessibility tobDMARDs. In this sense, we found that rural habitat andpoor county socioeconomic indicators (GDP/capita, numberof physicians/1000 inhabitants, and number of rheumatolo-gists/county) are associated with lower access to bDMARDs.In order to discuss the relevance of these results, we mustfirst review the characteristics of the sample. Compared topatients from other European RA registries [19], RA patientsfrom the RRRD have an equivalent mean age, the sameform of established disease according to disease duration,but a higher prevalence of female patients. In the absenceof conclusive epidemiological studies of RA in Romania, thisobservation may be explained by a number of competing rea-sons: underdiagnosis of men; higher disease severity amongwomen requiring biological therapy; a hypothesized geneticpopulation trait. Detailed prevalence studies are needed toassess these possibly non-mutually exclusive hypotheses.
Observational studies have reported that financial fac-
tors such as macroeconomic conditions, income, andnational health expenditure are major influencing factorsof bDMARD accessibility in European countries [11, 15,20–23]. Even though these studies made observations bycomparing different countries, it is reasonable to expect thatthe same financial factors influence bDMARD accessibilityof RA patients within different regions of the same country,given the existence of macroeconomic heterogeneity betweenthese regions. As EUROSTAT data show, the 41 countiesand the capital of Romania display an important amountof GDP/capita heterogeneity. Given these significant differ-
ences of GDP/capita among Romanian counties, we indeedshowed that low GDP/capita predicts low bDMARD access.Furthermore, even though national guidelines attempt tocreate equal opportunities in terms of access to biologictherapy for all eligible RA patients, in practice many patientsneed to travel to another county in order to benefit frombDMARDs. Finally, following its highest GDP/capita amongcounties, we observed a strong centralizing effect of thecapital on the number of RA patients treated with bDMARDs,a tendency noted by other authors in the literature [24]. Sinceevery county has its own Health Insurance House whichreimburses treatment cost, a revision of the distribution offunds would possibly increase accessibility to bDMARDsoutside the capital.
The observed predictive power of the number of physi-
cians/rheumatologists for bDMARD access of RA patients isintrinsically linked to the characteristics of the disease andthe structure of the health system. In this sense, the numberof physicians has been long used as an indicator of socioeco-nomic development. Nationwide, for a population of roughlytwenty million inhabitants, there were 235 active rheumatol-ogists. Out of the 42 administrative divisions of Romania,there were 7 counties without a rheumatologist, while in thecapital there were 75 active rheumatologists. The distributionof rheumatologists among the 41 counties and the capital wasuneven and it was correlated with territorial economic level,as measured by the GDP/county (rho = 0.731; 𝑝 < 0.001).

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While other more economically developed countries are also
facing a shortage of rheumatologists [25, 26], the proportionsare very different. The lack of specialized healthcare profes-s i o n a l si nr h e u m a t o l o g yl e a d st ok n o w nb a r r i e r st ob D M A R Dtherapy in RA, such as long waiting time for medical visitsand travel difficulties related to long distances to rheumatol-
ogy clinical settings [27, 28]. A study investigating patient-
reported barriers to access bDMARD treatment in RomanianRA patients would assess the full extent of the issue.
There are some limitations of this study which could
influence interpretation of the results. There were no dataregarding educational status (a known influencing factor ofbDMARD access) [15] and the actual extent of disease activityabove the protocol cutoff (DAS >5.1). A geographical con-
founder, which we were unable to control, can be described,namely, the travel distances to clinics between different coun-ties: these must have been patients who lived very close tocounty borders and therefore their extraterritorial bDMARDaccess could have been a matter of convenience. Additionalvariables (such as socioeconomic status of each patient andthe number of patients who did not receive biologics becauseof travelling limitations) were not collected. All the analyzedvariables came from different contributors to the RRRD (theattending rheumatologists) and their quality relies on theassumption of correct data input into the national electronicsystem.
5. Conclusions
In Romania, accessibility of RA patients to biological therapyvaries significantly between different counties. Areas withlow socioeconomic level do not offer equal and fair ther-apeutic opportunities for RA patients compared to othernational areas: patients with RA living in urban areas andcounties/regions with high living standards are more likelyto receive biological agents locally than those living inmore deprived areas. Studies investigating patient-reportedbarriers to biologic therapy are needed in the Romanianpopulation.
Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgments
The authors would like to acknowledge the support ofthe Romanian Registry of Rheumatic Diseases, which usesunrestricted grants from AbbVie, Pfizer, MSD, Roche, UCB,and BMS.
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